WO2024008902A1 - Anti-ageing cosmetic care composition comprising caulerpin - Google Patents
Anti-ageing cosmetic care composition comprising caulerpin Download PDFInfo
- Publication number
- WO2024008902A1 WO2024008902A1 PCT/EP2023/068799 EP2023068799W WO2024008902A1 WO 2024008902 A1 WO2024008902 A1 WO 2024008902A1 EP 2023068799 W EP2023068799 W EP 2023068799W WO 2024008902 A1 WO2024008902 A1 WO 2024008902A1
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- WIPO (PCT)
- Prior art keywords
- agents
- caulerpine
- skin
- caulerpin
- aging
- Prior art date
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- PVWALMHWUOWPPA-RPLHEXBESA-N caulerpin Chemical compound COC(=O)C/1=C/C(C2=CC=CC=C2N2)=C2\C(C(=O)OC)=C/C2=C\1NC1=CC=CC=C21 PVWALMHWUOWPPA-RPLHEXBESA-N 0.000 title abstract description 26
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
- A61K8/4926—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having six membered rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
- A61K8/9706—Algae
- A61K8/9722—Chlorophycota or Chlorophyta [green algae], e.g. Chlorella
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/42—Colour properties
- A61K2800/43—Pigments; Dyes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/52—Stabilizers
- A61K2800/522—Antioxidants; Radical scavengers
Definitions
- the present invention relates to a cosmetic composition for anti-aging skin care, comprising caulerpine in a physiologically acceptable medium.
- said caulerpine is obtained from Caulerpa Racemosa .
- the invention also relates to a non-therapeutic method for anti-aging treatment of an area of the skin, comprising a step of topical application of the composition according to the invention.
- the invention also relates to a method for extracting and purifying caulerpin.
- the skin undergoes numerous modifications and degradations which result, at the tissue level, in a disorganization of the architecture of the epidermis, of the dermal junction. epidermal, dermis, as well as blood irrigation and innervation systems, and a slowing down or disruption of different cellular metabolisms, such as those involved in the balance of barrier function or involved in melanogenesis.
- aging thus results in an alteration of the physiology or metabolism of the main cell types such as fibroblasts of the dermis, keratinocytes of the epidermis, and also melanocytes.
- Intrinsic or chrono-biological aging corresponds to normal or physiological aging linked to age.
- Intrinsic aging results in particular in a slowdown in the renewal of epidermis cells and the appearance of fine lines or wrinkles.
- the biosynthesis of macromolecules such as collagen decreases with age, changing the mechanical properties of the dermis, resulting in skin sagging, one of the clinical signs of aging.
- Extrinsic aging corresponds to aging caused generally by the external environment and corresponds in particular to photoaging due to exposure to the sun.
- Photo-induced skin aging that is to say caused following exposure to the sun, is also called photo-aging or helioderma.
- Photoaging is the result, in the dermis, of the degradation of collagen fibers, resulting in clinical alterations such as thick wrinkles and the formation of soft, leathery skin. Skin aging is therefore accelerated by chronic exposure to UV rays.
- Extrinsic aging can also be due to smoking, a diet too rich in fat or even alcohol consumption. These elements notably influence the gradual change of the redox environment towards a pro-oxidant state, and thus contribute to a progressive change in endothelial factors leading to endothelial dysfunction.
- anti-aging cosmetic treatments intended to prevent and/or treat aging, in particular photo-aging and its signs, in particular to prevent the appearance of wrinkles and to visibly reduce the appearance of wrinkles. wrinkles already present, but also reduce or eliminate senescence spots (due to age).
- these cosmetic treatments we can cite, for example, the regular application of so-called “anti-aging” or “anti-wrinkle” lotions or creams, comprising different cosmetic active ingredients.
- the Applicant has thus unexpectedly identified a new cosmetic active ingredient allowing effective anti-aging skin care, caulerpine.
- the invention relates to a cosmetic composition for anti-aging skin care, comprising caulerpine in a physiologically acceptable medium.
- cosmetic composition is meant according to the invention a “non-therapeutic” composition, which is therefore not intended to treat a patient.
- the cosmetic composition according to the invention does not act as a medication for the treatment of various diseases such as acne, xerosis, psoriasis or even eczema, but makes it possible to improve the superficial visual appearance. of the skin, in order to give it a rejuvenated appearance.
- an effective quantity within the meaning of the present invention is meant a quantity sufficient to obtain the expected effect, which can be determined by those skilled in the art.
- Caulerpine is a yellow pigment metabolized by certain species of caulerpes.
- the Caulerpa genus, of the Caulerpaceae family is represented by 87 species of algae, called Caulerpes. They are mainly distributed in the southern hemisphere, with only seven species present in the Mediterranean, including four in the western basin : C. taxifolia, C. racemosa , C. prolifera and C. olliveri (1) .
- Certain species such as C. racemosa or C. taxifolia are today considered invasive species, their rapid proliferation negatively affecting the marine ecosystem.
- Caulerpa racemosa is a species where the plant has radial branches, with compact cylindrical ramules (2, 3).
- Caulerpa taxifolia, Caulerpa racemosa , Caulerpa prolifera , Caulerpa serralioides are all rich in secondary metabolites. They are known to develop effective strategies against grazers and epiphytes, by synthesizing repellent secondary metabolites (4). The latter have been widely studied since their introduction into the Mediterranean Sea, particularly those of C. taxifolia (1). The most represented are caulerpine, caulerpicin and caulerpenyne. Caulerpine is more specific to Caulerpa racemosa .
- Caulerpine is a so-called “bisindolic” alkaloid because it contains two indole groups linked together by an eight-carbon ring containing two carboxyl groups (5).
- caulerpine can be obtained by extraction with ethanol or dimethyl sulfoxide.
- caulerpine Another known technique for extracting caulerpine is as follows: Caulerpa ethanolic extract racemosa was chromatographed on a silica gel column and eluted successively with n-hexane, n-hexane-chloroform, chloroform, chloroform-methanol and pure methanol. Fractions eluted with hexane-chloroform (1:1) gave red crystals of caulerpine with chloroform.
- the caulerpine according to the invention is extracted by the following process:
- the sampled batches of algae are freeze-dried. Each batch, treated separately, is then crushed to produce a fine powder and extracted with ethanol at 96° under ultrasound (3 ⁇ 15 min) protected from air, light and at room temperature. Each batch is vacuum filtered to separate the algal skeleton from the filtrate. Each filtrate is evaporated under reduced pressure (T ⁇ 35°C) to produce a raw organic (+salts) ethanolic extract.
- Each raw organic extract was then taken up in a water/methanol mixture (30/70), then subjected to liquid/liquid extraction with solvents of increasing polarity: cyclohexane then dichloromethane and finally ethyl acetate.
- the dichloromethane fraction is the one which allows the majority of caulerpine to be extracted.
- a purification phase is carried out on the dichloromethane fractions, to obtain pure caulerpine.
- silica diol chromatographic columns are preferably used.
- Solvents of increasing polarity are preferably used: cyclohexane, ethyl acetate, methanol.
- the fractions containing caulerpine are then washed with cyclohexane.
- Caulerpine is thus obtained.
- the cyclohexane fraction can also be eluted in the same way to obtain caulerpine, but in smaller quantity.
- anti-aging skin care is meant that the composition which is the subject of the invention has a non-therapeutic technical effect making it possible to improve the visible appearance of the skin, preferably of the face, so that it appears younger.
- the composition according to the invention thus makes it possible to hydrate, plump, nourish, revitalize, smooth, regenerate, firm, smooth, detoxify the skin, brighten the complexion, reduce age marks. age, to smooth and/or reduce the visibility of fine lines and wrinkles.
- Said cosmetic composition according to the invention also makes it possible to lift the eye contour, to smooth the fragile areas around the eyes and the lips, to harmonize and make the complexion more radiant, to refresh the look and/or to reduce the bags under the eyes and/or dark circles.
- composition comprising caulerpine according to the invention allow regeneration of the dermis, an anti-wrinkle effect, restructuring and firming of the dermis, regeneration and cellular revitalization, and to improve and/or strengthen the barrier function of the skin.
- composition according to the invention comprising caulerpin has the effect, as illustrated in Example 2, of overexpressing by at least 50% the genes coding for the following proteins, linked to the synthesis and the extracellular matrix structure: COL1A1, FBN2, LOXL1, PLOD3.
- alpha-1 type I collagen encoded by the COL1A1 gene is the main component of type I collagen, the fibrillar collagen present in most connective tissues, including cartilage.
- Fibrillin 2 strengthens the elastic fibers of the Extracellular matrix. It allows the homogeneous transmission of forces from the epidermis to the dermis.
- Lysyl oxidase like 1 (LOXL1) is an enzyme that initiates the bond between microfibers and elastin and ensures the functionality of elastic fibers.
- Pro-Collagen-Lysine, 2-Oxoglutarate 5-Dioxygenase 3 is an enzyme essential for the stability of intermolecular bonds. It structures collagen fibers.
- composition according to the invention comprising caulerpin has the effect, as illustrated in Example 2, of overexpressing by at least 50% the genes coding for the following proteins, linked to cell cohesion and the basal lamina:CD44, PXN, SDC4.
- CD44 is the receptor for hyaluronic acid, also capable of interacting with collagens. It is involved in cell/cell and cell/extracellular matrix interactions.
- Paxillin is a cytoskeletal protein located on the cytoplasmic side of regions specialized for cell attachment to the extracellular matrix.
- Syndecan 4 is a dermal matrix proteoglycan having a role in cell adhesion but which also modulates the proliferation of dermal cells.
- composition according to the invention comprising caulerpin has the effect, as illustrated in Example 2, of overexpressing by at least 50% the genes coding for the following proteins, linked to survival, cell growth and renewal: HBEGF, INSR, TP63.
- heparin-linked EGF-like growth factor is a growth factor that participates in the renewal of the epidermis.
- the insulin receptor is involved in skin renewal, the synthesis of dermal constituents and epidermal differentiation.
- the TP63 protein is a protein involved in the renewal of keratinocytes and fibroblasts, it protects cells from senescence and participates in differentiation.
- glutaredoxin participates in the elimination of oxygen radicals.
- Heme oxygenase (HMOX1) is involved in resistance to environmental stresses. It acts as a cytoprotective enzyme.
- SOD2 Superoxide Dismutase 2
- composition according to the invention comprising caulerpin has the effect, as illustrated in Example 2, of overexpressing by at least 50% the genes coding for the following proteins, with cellular differentiation and function barrier: CASP14, IVL, LOR, TGM1.
- Caspase-14 (CASP14) is a protease that is mainly expressed in the suprabasal epidermal layers and activated during the formation of the stratum corneum. It is necessary for the breakdown of filaggrin into the skin's natural hydration factors.
- IVL Involucrin
- Loricrin is a precursor of the horny envelope, a marker of terminal differentiation
- TGM1 Transglutaminase 1
- TGM1 is a key differentiation enzyme that catalyzes the bond between stratum corneum precursors and the cell membrane. It promotes the formation of the skin barrier.
- caulerpine is extracted from Caulerpa Racemosa .
- Caulerpa racemosa includes several varieties, including cylindracea, laetevirens, and macrophysa.
- caulerpine is present in the anti-aging skin care cosmetic composition according to the invention at a concentration between 0.01% and 10%, preferably between 0.1% and 5%, of even more preferably 1%, by weight of the composition.
- said cosmetic composition comprises 0.01%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1, 8%, 1.9%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10% by weight of the caulerpine composition.
- composition according to the invention comprises a physiologically acceptable medium, that is to say compatible with the skin of the face and/or body.
- the medium used has a pleasant color, odor and feel and does not generate unacceptable discomfort (such as in particular tingling, tightness, redness), likely to dissuade the consumer from using this composition.
- the cosmetic composition according to the invention further comprises at least one cosmetically acceptable agent.
- said at least one cosmetically acceptable agent is chosen from soothing agents, restructuring agents, regenerating agents, revitalizing agents, sun filters, anti-wrinkle agents, moisturizing agents, anti-aging agents, surfactants, fatty substances, organic solvents, solubilizing agents, thickening and gelling agents, smoothing agents, agents reinforcing the firmness, elasticity and/or barrier effect of the skin, antioxidants, opacifiers, thermal waters, mattifying agents, chemical or mineral filters, trace elements, stabilizing agents, foaming agents, perfumes, ionic or non-ionic emulsifiers, fillers, sequestrants and chelators, perfumes, filters, oils essential, coloring materials, pigments, hydrophilic or lipophilic active ingredients, lipid vesicles encapsulating one or more active ingredients and/or preservatives.
- caulerpine is solubilized in at least one solubilizing agent chosen from: 2,3-butanediol, 1,2-hexanediol, ethyl acetate, 2-propanol, propylene glycol, pentylene glycol, and dichloromethane.
- solubilizing agent chosen from: 2,3-butanediol, 1,2-hexanediol, ethyl acetate, 2-propanol, propylene glycol, pentylene glycol, and dichloromethane.
- caulerpine is solubilized in a combination of solvents: 1,2-hexanediol/dichloromethane or pentylene glycol/dichloromethane, followed by an evaporation step under pressure to reduce dichloromethane.
- Dichloromethane would be used temporarily as a co-solvent to facilitate the solubilization of caulerpin in 1,2-hexanediol or pentylene glycol.
- sun filter or UV filter is meant an agent which helps protect the skin from UVA and/or UVB. As such, it constitutes a means of passive external photoprotection, functioning as an ultraviolet filter.
- UV filters There are two types of UV filters, present together or separately in marketed products, namely mineral filters such as zinc oxide, or titanium dioxide, in the form of microscopic powders which act by reflecting UV rays, and chemical filters, which are organic chemical compounds forming a mixture of several chromophores that absorb ultraviolet light (such as oxybenzone, butyl methoxydibenzoylmethane, octyl-methoxycinnamate, octyl salicylate). Each of the chromophores has a specific UV absorption band (hence narrow-band or wide-band filters).
- said sunscreen is chosen from homosalate, oxybenzone, ensulizole, ecamsul, avobenzone, benzylidene camphor sulfonic acid, octocrylene, polyacrylamidomethyl benzylidene camphor, octinoxate, peg 25-PABA, PABA, isomamyl p-methoxycinnamate, octyl triazone, drometrizole trisiloxane, diethylhexyl butamido triazone, ethylhexyl salicilate, ethylhexyl dimethyl PABA, 4-methylbenzylidene camphor, 3-benzylidene camphor, l 'octisalate, padimate o, isoamyl p-Methoxycinnamate, benzophenone-4, methylene bis-benzotriazolyl tetra- methylbutyl,
- said cosmetic composition is formulated in the form of a cream, an ointment, an ointment, a balm, a mask, a milk, a lotion, a serum, 'a spray, a paste, a foam, an aerosol, a stick, a shampoo, a conditioner, patches, an aqueous hydroalcoholic or oily solution, an oil-in-water or water-in-oil or multiple emulsion, an aqueous or oily gel, an anhydrous liquid, pasty or solid product, and/or a dispersion of oil in an aqueous phase at using spherules, these spherules being able to be polymeric nanoparticles such as nanospheres and nanocapsules or lipid vesicles of ionic and/or non-ionic type.
- the invention relates to a cosmetic process for anti-aging care of an area of the skin, preferably of the face, comprising a step of applying the composition according to the preceding claims to the skin, preferably of the face. face.
- topical application within the meaning of the present invention is meant an application to the skin (including the scalp).
- composition cosmetic according to the invention is applied to the skin area.
- the cosmetic composition according to the invention is applied once or twice a day, preferably twice a day, for at least 7 days, preferably at least 15 days, more preferably at least one month, and particularly preferably at least 2 months.
- the cosmetic composition is applied in the process according to the invention 2 times a day for at least 1 month, preferably 2 months.
- said area of the skin is the face.
- the invention relates to the use of the composition according to the invention for the anti-aging care of an area of the skin, preferably the face.
- the ultrasound treatment carried out in step b. comprises the application of one to five ultrasound sequences, preferably 2 to 4 sequences, even more preferably 3 ultrasound sequences.
- each sequence lasts between 1 and 30 minutes, preferably between 10 and 20 minutes, even more preferably 15 minutes.
- the power of the ultrasound is 40 KHz. This power ensures that almost all of the caulerpine has been extracted.
- ultrasound sequences is meant that the mixture obtained in step b. undergoes periods of ultrasound interspersed with pauses where said mixture is not subjected to ultrasound.
- three ultrasound sequences mean that a first ultrasound application is carried out, followed by a pause, then a second ultrasound application, followed by a pause, and finally a final ultrasound application.
- step d. evaporation of the filtrate is carried out under pressure, preferably between 10 and 15 mbar.
- step d. evaporation of the filtrate is carried out at a temperature between 28°C and 35°C.
- said purification step is carried out by chromatography.
- said purification step is carried out using silica diol chromatographic columns using the solvents: cyclohexane, ethyl acetate, methanol; followed by a cyclohexane washing step.
- extraction is meant according to the invention that the caulerpine is separated from the rest of the plant which contained it.
- purification is meant according to the invention the act of separating the desired substance(s) from the rest of the substances present.
- lyophilization is meant according to the invention the process of drying at low temperature making it possible to remove the water contained in a product. This consists of three stages: freezing then sublimation and finally desorption.
- grinding is meant according to the invention the action consisting of reducing a material, for example by mechanical action.
- incorporation of the crude extract into a 30/70% water/methanol mixture is meant that the crude extract obtained is mixed with a pre-prepared mixture comprising a 30/70% water/methanol mixture.
- liquid/liquid extraction is meant according to the invention an extraction by transfer between two liquid phases.
- the invention relates to a composition comprising caulerpine, for use in the treatment of mucous membranes.
- this composition for use makes it possible to treat damaged mucous membranes.
- mucosa is understood according to the invention the membrane which lines the cavities of the body (digestive tube, nasal cavity, bronchi, anus, etc.) which connects with the skin at the level of the natural orifices, and which is lubricated by the secretion of mucus.
- mucosal lesions may result from a disorder or disease; in the case of the intestinal mucosa, the lesion can be caused by irritable bowel syndrome.
- the extract can be administered topically or orally.
- the invention relates to a food supplement for oral intake comprising caulerpine in a physiologically acceptable medium.
- food supplement is meant a product capable of providing nutritional benefit.
- This supplement can be taken alone or formulated with other compounds in order to make the composition more attractive to consume by being more similar to a common food product.
- This supplement may be a contributing factor in preventing or reducing any superficial visceral pain problem that does not require therapeutic treatment.
- the food supplement is taken in one or more successive doses.
- the successive doses are separated by at least 12 hours, preferably by at least one day, more preferably by at least two days, even more preferably by at least 3 days, even more preferably by at least 4 days, even more preferably at least 5 days, even more preferably at least 6 days.
- the oral intake of the food supplement is made by capsules, capsules, tablets, powders, granules, oral solutions or suspensions.
- the oral intake of the nutritional supplement is carried out by food products, a drink, a food additive or a dairy product, containing said nutritional supplement.
- FIG 1 HPLC-UV chromatograms at 214 nm, 254 nm and 280 nm of the Cyclohexane (a), Dichloromethane (b) and Ethyl acetate (c) fractions (Macherey-Nagel propylphenyl-C18, 250 x 4.6 mm; 5 ⁇ m, gradient: CH3CN + 0.1% formic acid (FA), H2O + 0.1% FA, 10:90 to 100:0 in 30 min).
- a Cyclohexane
- b Dichloromethane
- c Ethyl acetate
- Example 1 Extraction process and purification of the crude extract of Caulerpa racemosa according to the invention:
- Each filtrate is evaporated under reduced pressure (T ⁇ 35°C) to produce a raw organic (+salts) ethanolic extract, a total of 233.7 g for the batches sampled in Saint Jean Cap/La Ciotat and a total of 166 .3 g for batches sampled in Agde.
- HPLC-DAD-DEDL and HPLC-UV-HRMS62 analyzes of the different fractions were carried out.
- the results in terms of HPLC-DAD-UV at 214 nm, 254 nm and 280 nm for the cyclohexane (a), dichloromethane (b) and ethyl acetate (c) factions were obtained and are presented in [Fig 1 ].
- the cyclohexane fraction mainly contains fatty substances, as well as pigments such as chlorophyll, very weakly detected by reversed phase HPLC.
- the dichloromethane fractions contain mainly caulerpin, as well as fatty substances co-eluted with caulerpin, while the ethyl acetate fractions seemed to contain mainly unidentified polar compounds.
- the residual water/methanol fraction seemed to contain mainly salts, as well as some unidentified polar compounds.
- the chromatographic columns are then analyzed by TLC (thin layer chromatography), in order to collect the tubes containing the caulerpin.
- TLC thin layer chromatography
- Other tubes with similar CMM analyzes were pooled to obtain fractions.
- caulerpin The isolation of caulerpin is confirmed by HPLC-DAD-DEDL, HPLC-UV-HRMS and NMR analyses.
- Example 2 Evaluation of the cosmetic composition for anti-aging skin care according to the invention, on gene expression in human skin explants.
- the objective of the study is to study the effectiveness of the composition according to the invention on a prospective ex-vivo model of cosmetogenomic type.
- Microfluidic RT-qPCR technology will be used.
- the chip used in this study makes it possible to analyze a product in triplicate versus 90 genes on skin explants.
- the test was carried out on skin explants: a skin biopsy bathed in a solid and nourishing matrix while its epidermal surface is kept in contact with air. The skin biopsy is firmly anchored in the matrix and sealed to prevent any lateral diffusion of formulation intended for topical application.
- the explants come from an abdominoplasty of a 50-year-old woman corresponding to a phototype of II on the Fitzpatrick scale.
- RNAs were then reverse-transcribed into cDNA.
- the specific preparation steps for the chip (96 genes) according to the Fluidigm protocol are undertaken.
- a pre-amplification step in the presence of all the primers used on the chip is carried out.
- Each preamplified cDNA sample is then placed in a 96-well plate following the plate plan with the mix allowing real-time PCR.
- each pair of primers is placed in a well following the plate plane. Then each mix is placed on either side of the chip. The two mixes are mixed by the IFC Controller then the chip is placed in the BioMark to carry out real-time PCR.
- each primer pair is verified for all conditions by analysis of the dissociation curves and problematic points presenting double peaks are removed from the analysis.
- Each CT is then returned to the reference genes and the control cell condition to calculate the ⁇ CT and the relative expression is calculated as a function of the ⁇ CT using the formula 2- ⁇ CT.
- the standard error of the mean (SEM) is calculated and the points with too large SEMs (>40% difference between the SEM and the mean of the 3 values) are removed from the analysis.
- the results are expressed as percentage of overexpression or underexpression compared to the reference condition.
- the genes are then classified by biological activity for easier reading.
- Caulerpin demonstrates an increase in the expression of numerous genes linked to cellular differentiation and barrier function.
- Caulerpin shows positive effects in anti-aging, particularly in cell differentiation and barrier function, antioxidant protection, cell survival, growth and renewal, and extracellular matrix synthesis and structure.
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Abstract
The present invention relates to a cosmetic composition for anti-ageing care of the skin, comprising caulerpin in a physiologically acceptable medium. The caulerpin is preferably obtained from Caulerpa racemosa. The invention also relates to a non-therapeutic method for anti-ageing care of a region of the skin, comprising a step of topical application of the composition according to the invention. Finally, according to another aspect, the invention also relates to a method for extracting and purifying caulerpin.
Description
La présente invention concerne une composition cosmétique pour le soin anti-âge de la peau, comprenant de la caulerpine dans un milieu physiologiquement acceptable. De manière préférée, ladite caulerpine est obtenue à partir de Caulerpa Racemosa. L’invention concerne également un procédé non-thérapeutique de soin anti-âge d’une zone de la peau, comprenant une étape d’application topique de la composition selon l’invention. Enfin, selon un autre aspect, l’invention concerne également une méthode d’extraction et de purification de la caulerpine. The present invention relates to a cosmetic composition for anti-aging skin care, comprising caulerpine in a physiologically acceptable medium. Preferably, said caulerpine is obtained from Caulerpa Racemosa . The invention also relates to a non-therapeutic method for anti-aging treatment of an area of the skin, comprising a step of topical application of the composition according to the invention. Finally, according to another aspect, the invention also relates to a method for extracting and purifying caulerpin.
Le maintien d'une apparence juvénile est de nos jours un souci constant. Au cours du temps, et notamment du vieillissement chronologique et/ou photo-induit, la peau subit de nombreuses modifications et dégradations qui se traduisent, au niveau tissulaire, par une désorganisation de l'architecture de l'épiderme, de la jonction dermo-épidermique, du derme, ainsi que des systèmes d'irrigation sanguine et d'innervation, et un ralentissement ou dérèglement de différents métabolismes cellulaires, tels que ceux mis en jeu dans l'équilibre de la fonction barrière ou impliqués dans la mélanogénèse. Au niveau cellulaire, le vieillissement se traduit ainsi par une altération de la physiologie ou du métabolisme des principaux types cellulaires tels que les fibroblastes du derme, des kératinocytes de l'épiderme, et également des mélanocytes. Maintaining a youthful appearance is a constant concern these days. Over time, and in particular chronological and/or photo-induced aging, the skin undergoes numerous modifications and degradations which result, at the tissue level, in a disorganization of the architecture of the epidermis, of the dermal junction. epidermal, dermis, as well as blood irrigation and innervation systems, and a slowing down or disruption of different cellular metabolisms, such as those involved in the balance of barrier function or involved in melanogenesis. At the cellular level, aging thus results in an alteration of the physiology or metabolism of the main cell types such as fibroblasts of the dermis, keratinocytes of the epidermis, and also melanocytes.
Le vieillissement cutané résulte de deux processus distincts et indépendants qui font intervenir des facteurs intrinsèques ou extrinsèques. Le vieillissement intrinsèque ou chrono-biologique correspond au vieillissement normal ou physiologique lié à l'âge. Skin aging results from two distinct and independent processes which involve intrinsic or extrinsic factors. Intrinsic or chrono-biological aging corresponds to normal or physiological aging linked to age.
Le vieillissement intrinsèque se traduit notamment par un ralentissement du renouvellement des cellules de l'épiderme et l'apparition de fines rides ou ridules. Au niveau du derme, la biosynthèse des macromolécules telles que le collagène diminue avec l'âge changeant les propriétés mécaniques du derme, d'où le relâchement cutané, un des signes cliniques du vieillissement. Intrinsic aging results in particular in a slowdown in the renewal of epidermis cells and the appearance of fine lines or wrinkles. In the dermis, the biosynthesis of macromolecules such as collagen decreases with age, changing the mechanical properties of the dermis, resulting in skin sagging, one of the clinical signs of aging.
Le vieillissement extrinsèque correspond au vieillissement provoqué d'une manière générale par l'environnement extérieur et correspond notamment au photo-vieillissement dû à l'exposition au soleil. Le vieillissement cutané photo-induit, c'est-à-dire provoqué suite à une exposition au soleil est encore nommé photo-vieillissement ou héliodermie. Le photo-vieillissement est le résultat, au niveau du derme, de la dégradation des fibres de collagène ayant notamment pour conséquence des altérations cliniques telles que des rides épaisses et la formation d'une peau molle et tannée. Le vieillissement de la peau est donc accéléré par une exposition chronique aux UVs. Le vieillissement extrinsèque peut également être dû au tabagisme, à une alimentation trop riche en graisse ou encore à la consommation d’alcool. Ces éléments influencent notamment le changement graduel de l’environnement redox vers un état pro-oxydant, et contribuent ainsi à un changement progressif des facteurs endothéliaux menant à la dysfonction endothéliale.Extrinsic aging corresponds to aging caused generally by the external environment and corresponds in particular to photoaging due to exposure to the sun. Photo-induced skin aging, that is to say caused following exposure to the sun, is also called photo-aging or helioderma. Photoaging is the result, in the dermis, of the degradation of collagen fibers, resulting in clinical alterations such as thick wrinkles and the formation of soft, leathery skin. Skin aging is therefore accelerated by chronic exposure to UV rays. Extrinsic aging can also be due to smoking, a diet too rich in fat or even alcohol consumption. These elements notably influence the gradual change of the redox environment towards a pro-oxidant state, and thus contribute to a progressive change in endothelial factors leading to endothelial dysfunction.
Il existe ainsi un grand nombre de soins cosmétiques dits « anti-âge » destinés à prévenir et/ou traiter le vieillissement, en particulier le photo-vieillissement et leurs signes, notamment à prévenir l'apparition des rides et à réduire de façon visible les rides déjà présentes, mais aussi atténuer ou supprimer les tâches de sénescence (dues à l’âge). Parmi ces soins cosmétiques on peut citer, par exemple, l'application régulière de lotions ou de crèmes dites « anti-âge » ou « antirides », comprenant différents actifs cosmétiques. There are thus a large number of so-called "anti-aging" cosmetic treatments intended to prevent and/or treat aging, in particular photo-aging and its signs, in particular to prevent the appearance of wrinkles and to visibly reduce the appearance of wrinkles. wrinkles already present, but also reduce or eliminate senescence spots (due to age). Among these cosmetic treatments we can cite, for example, the regular application of so-called “anti-aging” or “anti-wrinkle” lotions or creams, comprising different cosmetic active ingredients.
Il perdure néanmoins le besoin constant de nouveaux actifs anti-âge efficaces à inclure dans des compositions cosmétiques de soin de la peau.However, there remains a constant need for new effective anti-aging active ingredients to be included in cosmetic skin care compositions.
La Demanderesse a ainsi identifié de manière inattendue un nouvel actif cosmétique permettant un soin anti-âge de la peau efficace, la caulerpine. The Applicant has thus unexpectedly identified a new cosmetic active ingredient allowing effective anti-aging skin care, caulerpine.
Ainsi, selon un premier aspect, l’invention concerne une composition cosmétique pour le soin anti-âge de la peau, comprenant de la caulerpine dans un milieu physiologiquement acceptable.Thus, according to a first aspect, the invention relates to a cosmetic composition for anti-aging skin care, comprising caulerpine in a physiologically acceptable medium.
Par « composition cosmétique » est entendu selon l’invention une composition « non-thérapeutique », qui n’a donc pas vocation à traiter un patient. De fait, la composition cosmétique selon l’invention n’agit pas comme un médicament pour le traitement de diverses maladies telles que l’acné, la xérose, le psoriasis ou encore l’eczéma, mais permet d’améliorer l’aspect visuel superficiel de la peau, afin de lui donner un aspect rajeunit.By “cosmetic composition” is meant according to the invention a “non-therapeutic” composition, which is therefore not intended to treat a patient. In fact, the cosmetic composition according to the invention does not act as a medication for the treatment of various diseases such as acne, xerosis, psoriasis or even eczema, but makes it possible to improve the superficial visual appearance. of the skin, in order to give it a rejuvenated appearance.
Les ingrédients de ladite composition cosmétique pour le soin anti-âge de la peau sont combinés dans des quantités efficaces. Par « quantité efficace », on entend au sens de la présente invention une quantité suffisante pour obtenir l'effet attendu, pouvant être déterminé par l’Homme du métier. The ingredients of said cosmetic composition for anti-aging skin care are combined in effective amounts. By “effective quantity”, within the meaning of the present invention is meant a quantity sufficient to obtain the expected effect, which can be determined by those skilled in the art.
La caulerpine est un pigment jaune métabolisé par certaines espèces de caulerpes. Le genre Caulerpa, de la famille des Caulerpaceae, est représenté par 87 espèces d’algues, appelées les Caulerpes. Elles sont très majoritairement réparties dans l’hémisphère sud, seules sept espèces étant présentes en Méditerranée dont quatre dans le bassin occidental : C. taxifolia, C. racemosa , C. prolifera et C. olliveri (1). Certaines espèces telles que C. racemosa ou C. taxifolia sont aujourd’hui considérées comme espèces invasives, leur prolifération fulgurante affectant négativement l’écosystème marin. Caulerpa racemosa est une espèce où la plante a des ramifications radiales, avec des ramules cylindriques compactes (2, 3).Caulerpine is a yellow pigment metabolized by certain species of caulerpes. The Caulerpa genus, of the Caulerpaceae family, is represented by 87 species of algae, called Caulerpes. They are mainly distributed in the southern hemisphere, with only seven species present in the Mediterranean, including four in the western basin : C. taxifolia, C. racemosa , C. prolifera and C. olliveri (1) . Certain species such as C. racemosa or C. taxifolia are today considered invasive species, their rapid proliferation negatively affecting the marine ecosystem. Caulerpa racemosa is a species where the plant has radial branches, with compact cylindrical ramules (2, 3).
Caulerpa taxifolia, Caulerpa racemosa , Caulerpa prolifera , Caulerpa sertularioides sont toutes riches en métabolites secondaires. Elles sont connues pour développer des stratégies efficaces contre les brouteurs et les épiphytes, en synthétisant des métabolites secondaires répulsifs (4). Ces derniers ont largement été étudiés depuis leur introduction en mer Méditerranée, notamment ceux de C. taxifolia (1). Les plus représentées sont la caulerpine, la caulerpicine et la caulerpényne. La caulerpine est plus spécifique de Caulerpa racemosa. Caulerpa taxifolia, Caulerpa racemosa , Caulerpa prolifera , Caulerpa serralioides are all rich in secondary metabolites. They are known to develop effective strategies against grazers and epiphytes, by synthesizing repellent secondary metabolites (4). The latter have been widely studied since their introduction into the Mediterranean Sea, particularly those of C. taxifolia (1). The most represented are caulerpine, caulerpicin and caulerpenyne. Caulerpine is more specific to Caulerpa racemosa .
La caulerpine est un alcaloïde dit « bisindolique » car il contient deux groupes indoles reliés entre eux par un cycle de huit carbones contenant deux groupes carboxyles (5). Caulerpine is a so-called “bisindolic” alkaloid because it contains two indole groups linked together by an eight-carbon ring containing two carboxyl groups (5).
Structure chimique de la caulerpine.Chemical structure of caulerpine.
Trois métabolites isolés de C. racemosa se distinguent par les points suivants :
- La CLP (I) (Mw = 398 g.mol-1) a été isolée à partir d’algues vertes (comme Codium decorticarum et Halimeda incrassate), dont 80 % des espèces de Caulerpa, ainsi qu’à partir de quelques algues rouges (dont Chondrus armatus (Harvey) Okamura) (6, 7, 8, 9). Les pourcentages de CLP I dans les différentes espèces de Caulerpa seraient : 15 % pour C. lentilifera, 5 % pour C. racemosa, 2 % pour C. microphysa et 8 % pour C. sertulariodes (10). Néanmoins, ces taux, sans doute surévalués, dépendent probablement d’autres facteurs comme l’origine géographique, l’ensoleillement ou le substrat. Des quantités allant de 1 à 5.47 mg par gramme d’algue pour les espèces C. cupressoides, C. paspaloides, C. prolifera et C. sertulaioides ont été trouvées (17).
- La CLP (II) (mW = 370 g.mol-1) est un diacide, qui se présente sous la forme de copeaux de couleur rouge à brun sombre. Sa température de fusion est comprise entre 254 et 256 °C
- La CLP (III) (Mw = 384 g.mol-1) est un pigment jaune orangé, qui se présente sous la forme d’aiguilles. Il ressemble à la caulerpine mais n’a qu’un seul groupement -CO2Me. Sa température de fusion est comprise entre 158 et 161 °C (5).
- CLP(I) (Mw = 398 g.mol-1) has been isolated from green algae (such as Codium decorticarum and Halimeda incrassate), including 80% of Caulerpa species, as well as from some red algae (including Chondrus armatus (Harvey) Okamura) (6, 7, 8, 9). The percentages of CLP I in the different Caulerpa species would be: 15% for C. lentilifera, 5% for C. racemosa, 2% for C. microphysa and 8% for C. serraliodes (10). However, these rates, undoubtedly overestimated, probably depend on other factors such as geographical origin, sunshine or substrate. Amounts ranging from 1 to 5.47 mg per gram of algae for the species C. cupressoides, C. paspaloides, C. prolifera and C. sertulaioides were found (17).
- CLP (II) (mW = 370 g.mol-1) is a diacid, which appears in the form of red to dark brown chips. Its melting temperature is between 254 and 256°C
- CLP (III) (Mw = 384 g.mol-1) is an orange-yellow pigment, which appears in the form of needles. It resembles caulerpin but has only one group -CO2Me. Its melting temperature is between 158 and 161°C (5).
De nombreuses méthodes d’extraction/purification de la caulerpine existent dans la littérature.Many caulerpine extraction/purification methods exist in the literature.
Pour la caulerpine, ces méthodes ont généralement en commun :
- Un passage par différents solvants (extraction) : il peut s’agir de méthanol (CH3OH), dichlorométhane (CH2Cl2), chloroforme, acétone (Me2CO), acétate d’éthyle (EtOAc), butanol (C4H10O), n-butanol (C4H9OH), hexane, n-hexane (C6H14)
- Une séparation sur une colonne chromatographique (purification) : les colonnes employées étant par exemple les colonnes Sephadex LH-20, Amberlite XAD 1180, Silica gel 60 Merck, ou Honsul
- Un passage dans un spectrophotomètre (identification).
- A passage through different solvents (extraction): it can be methanol (CH3OH), dichloromethane (CH2Cl2), chloroform, acetone (Me2CO), ethyl acetate (EtOAc), butanol (C4H10O), n-butanol (C4H9OH ), hexane, n-hexane (C6H14)
- Separation on a chromatographic column (purification): the columns used being for example the Sephadex LH-20, Amberlite XAD 1180, Silica gel 60 Merck, or Honsul columns
- A passage through a spectrophotometer (identification).
Selon un mode de réalisation, la caulerpine peut être obtenue par extraction à l’éthanol ou au diméthylsulfoxyde.According to one embodiment, caulerpine can be obtained by extraction with ethanol or dimethyl sulfoxide.
Des méthodes d’extraction de la caulerpine sont connues de l’Homme du métier et sont disponibles dans la littérature, notamment dans les documents indiqués dans la rubrique « Références ». . Methods for extracting caulerpine are known to those skilled in the art and are available in the literature, in particular in the documents indicated in the “References” section. .
Une autre technique connue d’extraction de la caulerpine est la suivante : L’extrait éthanolique de Caulerpa racemosa a été chromatographié sur une colonne de gel de silice et élué successivement avec du n-hexane, n-hexane-chloroforme, chloroforme, chloroforme-méthanol et pur méthanol. Les fractions éluées avec l’hexane-chloroforme (1:1) ont donné des cristaux rouges de caulerpine avec le chloroforme.Another known technique for extracting caulerpine is as follows: Caulerpa ethanolic extract racemosa was chromatographed on a silica gel column and eluted successively with n-hexane, n-hexane-chloroform, chloroform, chloroform-methanol and pure methanol. Fractions eluted with hexane-chloroform (1:1) gave red crystals of caulerpine with chloroform.
De manière préférée, la caulerpine selon l’invention est extraite par le procédé suivant : Les lots d’algues échantillonnés sont lyophilisés. Chaque lot, traité séparément, est ensuite broyé pour conduire à une fine poudre et extrait avec de l’éthanol à 96° sous ultrasons (3×15 min) à l’abris de l’air, de la lumière et à température ambiante. Chaque lot est filtré sous vide pour séparer le squelette de l’algue du filtrat. Chaque filtrat est évaporé sous pression réduite (T<35°C) pour conduire à un extrait brut organique (+sels) éthanolique. Chaque extrait brut organique a alors été repris dans un mélange eau/méthanol (30/70), puis soumis à une extraction liquide/liquide avec des solvants de polarité croissante : cyclohexane puis dichlorométhane et enfin acétate d’éthyle. La fraction dichlorométhane est celle qui permet d’extraire majoritairement la caulerpine.Preferably, the caulerpine according to the invention is extracted by the following process: The sampled batches of algae are freeze-dried. Each batch, treated separately, is then crushed to produce a fine powder and extracted with ethanol at 96° under ultrasound (3 × 15 min) protected from air, light and at room temperature. Each batch is vacuum filtered to separate the algal skeleton from the filtrate. Each filtrate is evaporated under reduced pressure (T<35°C) to produce a raw organic (+salts) ethanolic extract. Each raw organic extract was then taken up in a water/methanol mixture (30/70), then subjected to liquid/liquid extraction with solvents of increasing polarity: cyclohexane then dichloromethane and finally ethyl acetate. The dichloromethane fraction is the one which allows the majority of caulerpine to be extracted.
Sur les fractions dichlorométhane est réalisé une phase de purification, pour obtenir de la caulerpine pure. Pour cela, des colonnes chromatographiques silice diol sont de préférences utilisées. Des solvants de polarité croissante sont de préférence utilisées : cyclohexane, acetate d’éthyle, méthanol. Les fractions contenant la caulerpine sont ensuite lavées au moyen de cyclohexane. La caulerpine est ainsi obtenue.A purification phase is carried out on the dichloromethane fractions, to obtain pure caulerpine. For this, silica diol chromatographic columns are preferably used. Solvents of increasing polarity are preferably used: cyclohexane, ethyl acetate, methanol. The fractions containing caulerpine are then washed with cyclohexane. Caulerpine is thus obtained.
De manière alternative, la fraction cyclohexane peut également être éluée de la même façon pour obtenir de la caulerpine, mais en plus petite quantité. Alternatively, the cyclohexane fraction can also be eluted in the same way to obtain caulerpine, but in smaller quantity.
Ce type d’extraction et de purification est détaillée dans l’Exemple 1.This type of extraction and purification is detailed in Example 1.
Par « soin anti-âge de la peau » est entendu que la composition objet de l’invention a un effet technique non-thérapeutique permettant d’améliorer l’aspect visible de la peau, de préférence du visage, afin que celle-ci paraisse plus jeune. La composition selon l’invention permet ainsi d’hydrater, de repulper, de nourrir, de revitaliser, de lisser, de régénérer, de raffermir, de défroisser, de détoxifier la peau, d’illuminer le teint, d’atténuer les marques de l’âge, de lisser et/ou réduire la visibilité des rides et ridules. Ladite composition cosmétique selon l’invention permet également de lifter le contour des yeux, de lisser les zones fragiles du contour des yeux et des lèvres, d’harmoniser et de rendre le teint plus éclatant, de rafraichir le regard et/ou de réduire les poches sous les yeux et/ou les cernes. By “anti-aging skin care” is meant that the composition which is the subject of the invention has a non-therapeutic technical effect making it possible to improve the visible appearance of the skin, preferably of the face, so that it appears younger. The composition according to the invention thus makes it possible to hydrate, plump, nourish, revitalize, smooth, regenerate, firm, smooth, detoxify the skin, brighten the complexion, reduce age marks. age, to smooth and/or reduce the visibility of fine lines and wrinkles. Said cosmetic composition according to the invention also makes it possible to lift the eye contour, to smooth the fragile areas around the eyes and the lips, to harmonize and make the complexion more radiant, to refresh the look and/or to reduce the bags under the eyes and/or dark circles.
De manière plus spécifique, la composition selon l’invention démontre :
- un effet anti-âge curatif non-thérapeutique via un effet bénéfique sur :
- un effet anti-âge curatif non-thérapeutique via un effet bénéfique sur :
- la synthèse et la structure de la matrice extracellulaire ;
- la cohésion cellulaire et la lame basale ;
- un effet anti-âge préventif non-thérapeutique via un effet bénéfique sur : - la survie, la croissance et le renouvellement cellulaire ;
- la protection antioxydante ;
- un effet anti-âge préventif et curatif non-thérapeutique via un effet bénéfique, en lien avec la différenciation cellulaire et la fonction barrière.
- a non-therapeutic curative anti-aging effect via a beneficial effect on:
- the synthesis and structure of the extracellular matrix;
- cellular cohesion and the basal lamina;
- a non-therapeutic preventive anti-aging effect via a beneficial effect on: - cell survival, growth and renewal;
- antioxidant protection;
- a non-therapeutic preventive and curative anti-aging effect via a beneficial effect, linked to cellular differentiation and barrier function.
Ainsi, les effets rapportés de la composition comprenant de la caulerpine selon l’invention permettent une régénération du derme, un effet antiride, la restructuration et le raffermissement du derme, une régénération et une revitalisation cellulaire, et d’améliorer et/ou renforcer la fonction barrière de la peau.Thus, the reported effects of the composition comprising caulerpine according to the invention allow regeneration of the dermis, an anti-wrinkle effect, restructuring and firming of the dermis, regeneration and cellular revitalization, and to improve and/or strengthen the barrier function of the skin.
En particulier, la composition selon l’invention comprenant de la caulerpine a pour effet, tel qu’illustré dans l’Exemple 2, de surexprimer d’au moins 50% les gènes codant pour les protéines suivantes, en lien avec la synthèse et la structure de la matrice extracellulaire : COL1A1, FBN2, LOXL1, PLOD3. In particular, the composition according to the invention comprising caulerpin has the effect, as illustrated in Example 2, of overexpressing by at least 50% the genes coding for the following proteins, linked to the synthesis and the extracellular matrix structure: COL1A1, FBN2, LOXL1, PLOD3.
De manière plus spécifique, le collagène alpha-1 de type I codée par le gène COL1A1 est le composant principal du collagène de type I, le collagène fibrillaire présent dans la plupart des tissus conjonctifs, y compris le cartilage.More specifically, alpha-1 type I collagen encoded by the COL1A1 gene is the main component of type I collagen, the fibrillar collagen present in most connective tissues, including cartilage.
La Fibrilline 2 (FBN2) renforce les fibres élastiques de la matrice Extracellulaire. Elle permet la transmission homogène des forces de l’épiderme au derme. Fibrillin 2 (FBN2) strengthens the elastic fibers of the Extracellular matrix. It allows the homogeneous transmission of forces from the epidermis to the dermis.
La Lysyl oxydase like 1 (LOXL1) est une enzyme qui initie la liaison entre les microfibres et l’élastine et assure la fonctionnalité des fibres élastiques.Lysyl oxidase like 1 (LOXL1) is an enzyme that initiates the bond between microfibers and elastin and ensures the functionality of elastic fibers.
La Pro-Collagène-Lysine, 2-Oxoglutarate 5-Dioxygénase 3 (PLOD3) est une enzyme essentielle à la stabilité des liaisons intermoléculaire. Elle structure les fibres de collagène. Pro-Collagen-Lysine, 2-Oxoglutarate 5-Dioxygenase 3 (PLOD3) is an enzyme essential for the stability of intermolecular bonds. It structures collagen fibers.
En particulier, la composition selon l’invention comprenant de la caulerpine a pour effet, tel qu’illustré dans l’Exemple 2, de surexprimer d’au moins 50% les gènes codant pour les protéines suivantes, en lien avec la cohésion cellulaire et la lame basale :CD44, PXN, SDC4. In particular, the composition according to the invention comprising caulerpin has the effect, as illustrated in Example 2, of overexpressing by at least 50% the genes coding for the following proteins, linked to cell cohesion and the basal lamina:CD44, PXN, SDC4.
CD44 est le récepteur de l’acide hyaluronique, également capable d’interagir avec les collagènes. Il est impliqué dans les interactions cellule/cellule et cellules/matrice extracellulaire.CD44 is the receptor for hyaluronic acid, also capable of interacting with collagens. It is involved in cell/cell and cell/extracellular matrix interactions.
La Paxilline (PXN) est une protéine du cytosquelette située sur la face cytoplasmique des régions spécialisées pour l'attachement des cellules à la matrice extracellulaire.Paxillin (PXN) is a cytoskeletal protein located on the cytoplasmic side of regions specialized for cell attachment to the extracellular matrix.
Le Syndécan 4 (SDC4) est un protéoglycane de la matrice dermique ayant un rôle dans l'adhésion cellulaire mais qui module également la prolifération des cellules du derme. Syndecan 4 (SDC4) is a dermal matrix proteoglycan having a role in cell adhesion but which also modulates the proliferation of dermal cells.
En particulier, la composition selon l’invention comprenant de la caulerpine a pour effet, tel qu’illustré dans l’Exemple 2, de surexprimer d’au moins 50% les gènes codant pour les protéines suivantes, en lien avec la survie, la croissance et le renouvellement cellulaire : HBEGF, INSR, TP63. In particular, the composition according to the invention comprising caulerpin has the effect, as illustrated in Example 2, of overexpressing by at least 50% the genes coding for the following proteins, linked to survival, cell growth and renewal: HBEGF, INSR, TP63.
De manière plus spécifique, le facteur de croissance de type EGF lié à l'héparine (HBEGF) est un facteur de croissance qui participe au renouvellement de l'épiderme.More specifically, heparin-linked EGF-like growth factor (HBEGF) is a growth factor that participates in the renewal of the epidermis.
Le récepteur de l’insuline (INSR) est impliqué dans le renouvellement de la peau, la synthèse des constituants du derme et la différenciation épidermique.The insulin receptor (INSR) is involved in skin renewal, the synthesis of dermal constituents and epidermal differentiation.
La protéine TP63 est une protéine impliquée dans le renouvellement des kératinocytes et des fibroblastes, elle protège les cellules de la senescence et participe à la différenciation. The TP63 protein is a protein involved in the renewal of keratinocytes and fibroblasts, it protects cells from senescence and participates in differentiation.
En particulier, la composition selon l’invention comprenant de la caulerpine a pour effet, tel qu’illustré dans l’Exemple 2, de surexprimer d’au moins 50% les gènes codant pour les protéines suivantes, en lien avec protection antioxydante : GLRX, HMOX1, SOD2. In particular, the composition according to the invention comprising caulerpin has the effect, as illustrated in Example 2, of overexpressing by at least 50% the genes coding for the following proteins, linked to antioxidant protection: GLRX , HMOX1, SOD2.
De manière plus spécifiques, la glutaredoxine (GLRX) participe à l'élimination des radicaux oxygénés.More specifically, glutaredoxin (GLRX) participates in the elimination of oxygen radicals.
L'hème oxygénase (HMOX1) est impliquée dans la résistance aux stress environnementaux. Elle agit comme une enzyme cytoprotectrice.Heme oxygenase (HMOX1) is involved in resistance to environmental stresses. It acts as a cytoprotective enzyme.
La Superoxyde Dismutase 2 (SOD2) est une enzyme mitochondriale ayant une activité antioxydante. Elle est également connue pour réduire la pigmentation induite par les UV Superoxide Dismutase 2 (SOD2) is a mitochondrial enzyme with antioxidant activity. It is also known to reduce UV-induced pigmentation
En particulier, la composition selon l’invention comprenant de la caulerpine a pour effet, tel qu’illustré dans l’Exemple 2, de surexprimer d’au moins 50% les gènes codant pour les protéines suivantes, avec la différenciation cellulaire et la fonction barrière : CASP14, IVL, LOR, TGM1. In particular, the composition according to the invention comprising caulerpin has the effect, as illustrated in Example 2, of overexpressing by at least 50% the genes coding for the following proteins, with cellular differentiation and function barrier: CASP14, IVL, LOR, TGM1.
De manière plus spécifique, la Caspase-14 (CASP14) est une protéase qui est principalement exprimée dans les couches épidermiques suprabasales et activée lors de la formation de la couche cornée. Elle est nécessaire à la dégradation de la filaggrine en facteurs d'hydratation naturels de la peau. More specifically, Caspase-14 (CASP14) is a protease that is mainly expressed in the suprabasal epidermal layers and activated during the formation of the stratum corneum. It is necessary for the breakdown of filaggrin into the skin's natural hydration factors.
L'Involucrine (IVL) est une protéine essentielle de la couche cornée qui active la fonction barrière.Involucrin (IVL) is an essential protein of the stratum corneum which activates the barrier function.
La Loricrine (LOR) est un précurseur de l'enveloppe cornée, marqueur de la différenciation terminale Loricrin (LOR) is a precursor of the horny envelope, a marker of terminal differentiation
La Transglutaminase 1 (TGM1) est une enzyme clé de la différenciation qui catalyse la liaison entre les précurseurs de la couche cornée et la membrane cellulaire. Elle favorise la formation de la barrière cutanée. Transglutaminase 1 (TGM1) is a key differentiation enzyme that catalyzes the bond between stratum corneum precursors and the cell membrane. It promotes the formation of the skin barrier.
De manière préférée selon l’invention, la caulerpine est extraite de Caulerpa Racemosa . Caulerpa racemosa comprend plusieurs variétés, dont cylindracea, laetevirens, et macrophysa.
Preferably according to the invention, caulerpine is extracted from Caulerpa Racemosa . Caulerpa racemosa includes several varieties, including cylindracea, laetevirens, and macrophysa.
Selon un mode de réalisation, la caulerpine est présente dans la composition cosmétique de soin anti-âge de la peau selon l’invention à une concentration entre 0,01 % et 10 %, de préférence entre 0,1% et 5 %, de manière encore plus préférée 1%, en poids de la composition.According to one embodiment, caulerpine is present in the anti-aging skin care cosmetic composition according to the invention at a concentration between 0.01% and 10%, preferably between 0.1% and 5%, of even more preferably 1%, by weight of the composition.
Selon un mode de réalisation, ladite composition cosmétique comprend 0,01%, 0,1%, 0,2%, 0,3%, 0,4%, 0,5%, 0,6%, 0,7%, 0,8%, 0,9%, 1%, 1,1%, 1,2%, 1,3%, 1,4%, 1,5%, 1,6%, 1,7%, 1,8%, 1,9%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, ou 10% en poids de la composition de caulerpine.According to one embodiment, said cosmetic composition comprises 0.01%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1, 8%, 1.9%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10% by weight of the caulerpine composition.
La composition selon l'invention comprend un milieu physiologiquement acceptable, c'est-à-dire compatible avec la peau du visage et/ou du corps. En d'autres termes, le milieu utilisé présente une couleur, une odeur et un toucher agréables et ne génère pas d'inconforts inacceptables (tels que notamment picotements, tiraillements, rougeurs), susceptibles de détourner le consommateur d'utiliser cette composition.The composition according to the invention comprises a physiologically acceptable medium, that is to say compatible with the skin of the face and/or body. In other words, the medium used has a pleasant color, odor and feel and does not generate unacceptable discomfort (such as in particular tingling, tightness, redness), likely to dissuade the consumer from using this composition.
Selon un mode de réalisation, la composition cosmétique selon l’invention comprend en outre au moins un agent cosmétiquement acceptable.According to one embodiment, the cosmetic composition according to the invention further comprises at least one cosmetically acceptable agent.
De manière préférée, ledit au moins un agent cosmétiquement acceptable est choisi parmi les agents apaisants, les agents restructurant, les agents régénérants, les agents revitalisants, les filtres solaires, les agents antirides, les agents hydratants, les agents anti-âges, les agents tensioactifs, les corps gras, les solvants organiques, les agents solubilisant, les agents épaississants et gélifiants, les lissants, les agents renforçant la fermeté, l’élasticité et/ou l’effet barrière de la peau, les antioxydants, les opacifiants, les eaux thermales, les agents matifiants, les filtres chimiques ou minéraux, les oligoéléments, les agents stabilisants, les agents moussants, les parfums, les émulsionnants ioniques ou non, les charges, les séquestrants et les chélateurs, les parfums, les filtres, les huiles essentielles, les matières colorantes, les pigments, les actifs hydrophiles ou lipophiles, les vésicules lipidiques encapsulant un ou plusieurs actifs et/ou les conservateurs.Preferably, said at least one cosmetically acceptable agent is chosen from soothing agents, restructuring agents, regenerating agents, revitalizing agents, sun filters, anti-wrinkle agents, moisturizing agents, anti-aging agents, surfactants, fatty substances, organic solvents, solubilizing agents, thickening and gelling agents, smoothing agents, agents reinforcing the firmness, elasticity and/or barrier effect of the skin, antioxidants, opacifiers, thermal waters, mattifying agents, chemical or mineral filters, trace elements, stabilizing agents, foaming agents, perfumes, ionic or non-ionic emulsifiers, fillers, sequestrants and chelators, perfumes, filters, oils essential, coloring materials, pigments, hydrophilic or lipophilic active ingredients, lipid vesicles encapsulating one or more active ingredients and/or preservatives.
De manière préférée, la caulerpine est solubilisée dans au moins un agent solubilisant choisi parmi : 2,3-butanediol, le 1,2-hexanediol, l’acétate d’éthyle, le 2-propanol, le propylène glycol, le pentylène glycol, et le dichlorométhane. Preferably, caulerpine is solubilized in at least one solubilizing agent chosen from: 2,3-butanediol, 1,2-hexanediol, ethyl acetate, 2-propanol, propylene glycol, pentylene glycol, and dichloromethane.
De manière préférée, la caulerpine est solubilisée dans une association des solvants : 1,2-hexanediol/dichlorométhane ou pentylène glycol/dichlorométhane, suivi d’une étape d’évaporation sous pression réduire du dichlorométhane. Le dichlorométhane serait utilisé de façon temporaire en guise de co-solvant afin de faciliter la solubilisation de la caulerpine dans le 1,2-hexanediol ou le pentylène glycol. Preferably, caulerpine is solubilized in a combination of solvents: 1,2-hexanediol/dichloromethane or pentylene glycol/dichloromethane, followed by an evaporation step under pressure to reduce dichloromethane. Dichloromethane would be used temporarily as a co-solvent to facilitate the solubilization of caulerpin in 1,2-hexanediol or pentylene glycol.
Par filtre solaire ou filtre UV est entendu un agent qui permet de protéger la peau des UVA et/ou des UVB. Elle constitue à ce titre un moyen de photoprotection externe passive, fonctionnant comme un filtre ultraviolet. Il existe deux types de filtres UV, présent ensemble ou séparément dans les produits commercialisés, à savoir les filtres minéraux comme l’oxyde de zinc, ou le dioxyde de titane, se présentant sous forme de poudres microscopiques qui agissent en réfléchissant les rayons UV, et les filtres chimiques, qui sont des composés chimiques organiques formant un mélange de plusieurs chromophores qui absorbent la lumière ultraviolette (comme l'oxybenzone, le butyl méthoxydibenzoylméthane, l’octyl-méthoxycinnamate, le salicylate d'octyle). Chacun des chromophores possède une bande d'absorption d'UV spécifique (d'où les filtres à bande étroite ou à large bande).By sun filter or UV filter is meant an agent which helps protect the skin from UVA and/or UVB. As such, it constitutes a means of passive external photoprotection, functioning as an ultraviolet filter. There are two types of UV filters, present together or separately in marketed products, namely mineral filters such as zinc oxide, or titanium dioxide, in the form of microscopic powders which act by reflecting UV rays, and chemical filters, which are organic chemical compounds forming a mixture of several chromophores that absorb ultraviolet light (such as oxybenzone, butyl methoxydibenzoylmethane, octyl-methoxycinnamate, octyl salicylate). Each of the chromophores has a specific UV absorption band (hence narrow-band or wide-band filters).
De manière encore plus préférée, ledit filtre solaire est choisi parmi l’homosalate, l’oxybenzone, l’ensulizole, l’ecamsul, l’avobenzone, l’acide benzylidene camphor sulfonic, l’octocrylène, le polyacrylamidomethyl benzylidène camphor, l’ octinoxate, le peg 25-PABA, le PABA, l’isomamyl p- methoxycinnamate, l’octyl triazone, le drometrizole trisiloxane, diethylhexyl butamido triazone, ethylhexyl salicilate, ethylhexyl dimethyl PABA, 4-methylbenzylidene camphor, le 3-benzylidène camphor, l’octisalate, le padimate o, isoamyl p-Methoxycinnamate, benzophenone-4, le méthylène bis-benzotriazolyl tetra- methylbutylphenol, disodium phenyl dibenzimidazole tetrasulfonate, le bis-ethylhexyloxyphenol methoxyphenyl triazine, le polysilicone-15, le dioxyde de titane, l’oxyde de zinc, le butyl méthoxydibenzoylméthane, l’octyl-méthoxycinnamate, le salicylate d'octyle et/ou le diethylamino hydroxybenzoyl hexyl benzoate.Even more preferably, said sunscreen is chosen from homosalate, oxybenzone, ensulizole, ecamsul, avobenzone, benzylidene camphor sulfonic acid, octocrylene, polyacrylamidomethyl benzylidene camphor, octinoxate, peg 25-PABA, PABA, isomamyl p-methoxycinnamate, octyl triazone, drometrizole trisiloxane, diethylhexyl butamido triazone, ethylhexyl salicilate, ethylhexyl dimethyl PABA, 4-methylbenzylidene camphor, 3-benzylidene camphor, l 'octisalate, padimate o, isoamyl p-Methoxycinnamate, benzophenone-4, methylene bis-benzotriazolyl tetra- methylbutylphenol, disodium phenyl dibenzimidazole tetrasulfonate, bis-ethylhexyloxyphenol methoxyphenyl triazine, polysilicone-15, titanium dioxide, oxide zinc, butyl methoxydibenzoylmethane, octyl-methoxycinnamate, octyl salicylate and/or diethylamino hydroxybenzoyl hexyl benzoate.
De manière préférée, ladite composition cosmétique est formulé sous forme de crème, d'une pommade, d’un onguent, d’un baume, d’un masque, d'un lait, d'une lotion, d'un sérum, d’un spray, d'une pâte, d'une mousse, d'un aérosol, d’un stick, d’un shampooing, d’un après-shampooing, de patchs, d'une solution aqueuse hydroalcoolique ou huileuse, d'une émulsion huile-dans-eau ou eau-dans-huile ou multiple, d'un gel aqueux ou huileux, d'un produit anhydre liquide, pâteux ou solide, et/ou d'une dispersion d'huile dans une phase aqueuse à l'aide de sphérules, ces sphérules pouvant être des nanoparticules polymériques telles que les nanosphères et les nanocapsules ou des vésicules lipidiques de type ionique et/ou non-ionique.Preferably, said cosmetic composition is formulated in the form of a cream, an ointment, an ointment, a balm, a mask, a milk, a lotion, a serum, 'a spray, a paste, a foam, an aerosol, a stick, a shampoo, a conditioner, patches, an aqueous hydroalcoholic or oily solution, an oil-in-water or water-in-oil or multiple emulsion, an aqueous or oily gel, an anhydrous liquid, pasty or solid product, and/or a dispersion of oil in an aqueous phase at using spherules, these spherules being able to be polymeric nanoparticles such as nanospheres and nanocapsules or lipid vesicles of ionic and/or non-ionic type.
Selon un deuxième aspect, l’invention concerne un procédé cosmétique de soin anti-âge d’une zone de la peau, de préférence du visage, comprenant une étape d’application de la composition selon les revendications précédentes sur la peau, de préférence du visage. According to a second aspect, the invention relates to a cosmetic process for anti-aging care of an area of the skin, preferably of the face, comprising a step of applying the composition according to the preceding claims to the skin, preferably of the face. face.
Par « application topique », on entend au sens de la présente invention une application sur la peau (dont le cuir chevelu).By “topical application”, within the meaning of the present invention is meant an application to the skin (including the scalp).
De manière préférée, une quantité d’environ 0,1 à 50 mg/cm2, de préférence environ 0,25 à 25 mg/cm2, de manière encore plus préférée d’environ 2 à 10 mg/cm2, de composition cosmétique selon l’invention est appliqué sur la zone de la peau.Preferably, an amount of approximately 0.1 to 50 mg/cm 2 , preferably approximately 0.25 to 25 mg/cm 2 , even more preferably approximately 2 to 10 mg/cm 2 , of composition cosmetic according to the invention is applied to the skin area.
De manière préférée, la composition cosmétique selon l’invention est appliquée une à deux fois par jour, de préférence 2 fois par jour, pendant au moins 7 jours, de préférence au moins 15 jours, de manière encore préférée au moins un mois, et de manière particulièrement préférée au moins 2 mois. Preferably, the cosmetic composition according to the invention is applied once or twice a day, preferably twice a day, for at least 7 days, preferably at least 15 days, more preferably at least one month, and particularly preferably at least 2 months.
De manière tout particulièrement préférée, la composition cosmétique est appliquée dans le procédé selon l’invention 2 fois par jour pendant au moins 1 mois, de préférence 2 mois.Very particularly preferably, the cosmetic composition is applied in the process according to the invention 2 times a day for at least 1 month, preferably 2 months.
De manière préférée selon l’invention, ladite zone de la peau est le visage.Preferably according to the invention, said area of the skin is the face.
Selon un troisième aspect, l’invention concerne l’utilisation de la composition selon l’invention pour le soin anti-âge d’une zone de la peau, de préférence du visage. According to a third aspect, the invention relates to the use of the composition according to the invention for the anti-aging care of an area of the skin, preferably the face.
Selon un quatrième aspect, l’invention concerne une méthode d’extraction et de purification de la caulerpine comprenant les étapes de :
- Lyophilisation et broyage de plants de Caulerpa Racemosa, permettant l’obtention d’une poudre ;
- Extraction de la poudre par mise en contact avec de l’éthanol à 96° et traitement aux ultrasons, à l’abris de l’air, de la lumière et à température ambiante ;
- Filtration sous vide pour séparer le squelette de l’algue du filtrat ;
- Évaporation du filtrat pour obtenir un extrait brut éthanolique ;
- Incorporation de l’extrait brut dans un mélange eau/méthanol 30/70 % ;
- Extraction liquide/liquide avec successivement :
- un solvant cyclohexane ;
- un solvant dichlorométhane ; et
- un solvant l’acétate d’éthyle ;
- Purification de la fraction dichlorométhane, et optionnellement de la fraction cyclohexane ;
- Obtention de la caulerpine.
- Freeze drying and grinding of Caulerpa plants Racemosa , allowing a powder to be obtained;
- Extraction of the powder by contact with ethanol at 96° and treatment with ultrasound, protected from air, light and at room temperature;
- Vacuum filtration to separate the algae skeleton from the filtrate;
- Evaporation of the filtrate to obtain a crude ethanolic extract;
- Incorporation of the crude extract into a 30/70% water/methanol mixture;
- Liquid/liquid extraction with successively:
- a cyclohexane solvent;
- a dichloromethane solvent; And
- a solvent: ethyl acetate;
- Purification of the dichloromethane fraction, and optionally of the cyclohexane fraction;
- Obtaining caulerpine.
De manière préférée, le traitement aux ultrasons réalisé à l’étape b. comprend l’application d’une à cinq séquences d’ultrasons, de préférence 2 à 4 séquences, de manière encore plus préférée 3 séquences d’ultrasons.Preferably, the ultrasound treatment carried out in step b. comprises the application of one to five ultrasound sequences, preferably 2 to 4 sequences, even more preferably 3 ultrasound sequences.
De manière préférée, à l’étape b., chaque séquence dure entre 1 et 30 minutes, de manière préférée entre 10 et 20 minutes, de manière encore plus préférée 15 minutes.Preferably, in step b., each sequence lasts between 1 and 30 minutes, preferably between 10 and 20 minutes, even more preferably 15 minutes.
De manière préférée, à l’étape b., la puissance des ultrasons est de 40 KHz. Cette puissance permet de garantir que quasiment toute la caulerpine a été extraite.Preferably, in step b., the power of the ultrasound is 40 KHz. This power ensures that almost all of the caulerpine has been extracted.
Par « séquences d’ultrasons » est entendu que le mélange obtenu à l’étape b. subit des périodes d’ultrasons entrecoupées de pauses où ledit mélange n’est pas soumis aux ultrasons. Par exemple trois séquences d’ultrasons signifie qu’une première application d’ultrason est réalisée, suivie d’une pause, puis d’une deuxième application d’ultrason, suivie d’une pause, et enfin une dernière application d’ultrason.By “ultrasound sequences” is meant that the mixture obtained in step b. undergoes periods of ultrasound interspersed with pauses where said mixture is not subjected to ultrasound. For example, three ultrasound sequences mean that a first ultrasound application is carried out, followed by a pause, then a second ultrasound application, followed by a pause, and finally a final ultrasound application.
De manière préférée, l’étape d. d’évaporation du filtrat est réalisée sous pression, de préférence entre 10 et 15 mbar.Preferably, step d. evaporation of the filtrate is carried out under pressure, preferably between 10 and 15 mbar.
De manière préférée, l’étape d. d’évaporation du filtrat est réalisée à une température comprise entre 28°C et 35°C.Preferably, step d. evaporation of the filtrate is carried out at a temperature between 28°C and 35°C.
Selon un mode de réalisation, ladite étape de purification est réalisée par chromatographie. According to one embodiment, said purification step is carried out by chromatography.
Selon un mode de réalisation, ladite étape de purification est réalisée grâce à des colonnes chromatographiques silice diol en utilisant les solvants : cyclohexane, acétate d’éthyle, méthanol ; suivi d’une étape de lavage au cyclohexane.According to one embodiment, said purification step is carried out using silica diol chromatographic columns using the solvents: cyclohexane, ethyl acetate, methanol; followed by a cyclohexane washing step.
Par « extraction » est entendu selon l’invention que la caulerpine est séparée du reste de la plante qui la contenait. By “extraction” is meant according to the invention that the caulerpine is separated from the rest of the plant which contained it.
Par « purification » est entendu selon l’invention le fait de séparer, la (les) substance(s) voulue(s) du reste des substances présentes.By “purification” is meant according to the invention the act of separating the desired substance(s) from the rest of the substances present.
Par « lyophilisation » est entendu selon l’invention le processus de séchage à basse température permettant de retirer l'eau contenue dans un produit. Cela consiste en trois étapes : la congélation puis la sublimation et enfin la désorption.By “lyophilization” is meant according to the invention the process of drying at low temperature making it possible to remove the water contained in a product. This consists of three stages: freezing then sublimation and finally desorption.
Par « broyage » est entendu selon l’invention l’action consistant à réduire une matière, par exemple par action mécanique.By “grinding” is meant according to the invention the action consisting of reducing a material, for example by mechanical action.
Par « incorporation » de l’extrait brut dans un mélange eau/méthanol 30/70 % est entendu que l’extrait brut obtenu est mélangé avec un mélange pré-préparé comprenant mélange eau/méthanol 30/70 %By “incorporation” of the crude extract into a 30/70% water/methanol mixture is meant that the crude extract obtained is mixed with a pre-prepared mixture comprising a 30/70% water/methanol mixture.
Par « extraction liquide/liquide » est entendu selon l’invention une extraction par transfert entre deux phases liquides.By “liquid/liquid extraction” is meant according to the invention an extraction by transfer between two liquid phases.
Selon un cinquième aspect, l’invention concerne une composition comprenant de la caulerpine, pour utilisation dans le traitement des muqueuses.According to a fifth aspect, the invention relates to a composition comprising caulerpine, for use in the treatment of mucous membranes.
De manière préférée, cette composition pour utilisation permet de traiter les muqueuses lésées. Preferably, this composition for use makes it possible to treat damaged mucous membranes.
Par « muqueuse » est entendue selon l’invention la membrane qui tapisse les cavités de l'organisme (tube digestif, fosses nasales, bronches, anus…) qui se raccorde avec la peau au niveau des orifices naturels, et qui est lubrifiée par la sécrétion de mucus.By "mucosa" is understood according to the invention the membrane which lines the cavities of the body (digestive tube, nasal cavity, bronchi, anus, etc.) which connects with the skin at the level of the natural orifices, and which is lubricated by the secretion of mucus.
Ces lésions de la muqueuse peuvent résulter d'un trouble ou d'une maladie ; dans le cas de la muqueuse intestinale, la lésion peut être provoquée par le syndrome du côlon irritable. These mucosal lesions may result from a disorder or disease; in the case of the intestinal mucosa, the lesion can be caused by irritable bowel syndrome.
Dans cet aspect, l'extrait peut être administré par voie topique ou par voie orale.In this aspect, the extract can be administered topically or orally.
Selon un sixième aspect, l’invention concerne un complément alimentaire à prise orale comprenant de la caulerpine dans un milieu physiologiquement acceptable. According to a sixth aspect, the invention relates to a food supplement for oral intake comprising caulerpine in a physiologically acceptable medium.
Par " complément alimentaire ", on entend selon l'invention un produit pouvant apporter un bénéfice nutritionnel. Ce complément peut être pris seul ou être formulé avec d'autres composés afin de rendre la composition plus attrayante à consommer en étant plus similaire à un produit alimentaire courant. Ce complément peut être un facteur contribuant à prévenir ou à diminuer tout problème de douleur viscérale superficielle qui ne nécessite pas de traitement thérapeutique.By “food supplement”, according to the invention is meant a product capable of providing nutritional benefit. This supplement can be taken alone or formulated with other compounds in order to make the composition more attractive to consume by being more similar to a common food product. This supplement may be a contributing factor in preventing or reducing any superficial visceral pain problem that does not require therapeutic treatment.
Selon un mode de réalisation, la prise du complément alimentaire est effectuée par une ou plusieurs doses successives.According to one embodiment, the food supplement is taken in one or more successive doses.
Selon un mode de réalisation, les doses successives sont séparées d'au moins 12 heures, de préférence d'au moins un jour, plus préférablement d'au moins deux jours, encore plus préférablement d'au moins 3 jours, encore plus préférablement d'au moins 4 jours, encore plus préférablement d'au moins 5 jours, encore plus préférablement d'au moins 6 jours.According to one embodiment, the successive doses are separated by at least 12 hours, preferably by at least one day, more preferably by at least two days, even more preferably by at least 3 days, even more preferably by at least 4 days, even more preferably at least 5 days, even more preferably at least 6 days.
Selon un mode de réalisation, la prise orale du complément alimentaire est faite par des capsules, des gélules, des comprimés, des poudres, des granules, des solutions orales ou des suspensions.According to one embodiment, the oral intake of the food supplement is made by capsules, capsules, tablets, powders, granules, oral solutions or suspensions.
Selon un mode de réalisation, la prise orale du complément nutritionnel est effectuée par des produits alimentaires, une boisson, un additif alimentaire ou un produit laitier, contenant ledit complément nutritionnel.According to one embodiment, the oral intake of the nutritional supplement is carried out by food products, a drink, a food additive or a dairy product, containing said nutritional supplement.
[Fig 1] : Chromatogrammes HPLC-UV à 214 nm, 254 nm et 280 nm des fractions Cyclohexane (a), Dichlorométhane (b) et Acétate d’éthyle (c) (Macherey-Nagel propylphényl-C18, 250 x 4,6 mm ; 5 μm, gradient : CH3CN + 0,1% d’acide formique (AF), H2O + 0,1% AF, 10:90 à 100:0 en 30 mn).[Fig 1]: HPLC-UV chromatograms at 214 nm, 254 nm and 280 nm of the Cyclohexane (a), Dichloromethane (b) and Ethyl acetate (c) fractions (Macherey-Nagel propylphenyl-C18, 250 x 4.6 mm; 5 μm, gradient: CH3CN + 0.1% formic acid (FA), H2O + 0.1% FA, 10:90 to 100:0 in 30 min).
Exemple 1 : Procédé d’extraction Example 1: Extraction process
et de purification and purification
de l’extrait brut de of the crude extract of
CaulerpaCaulerpa
racemosa racemosa
selon l’invention : according to the invention:
ExtractionExtraction
Des lots d’algues échantillonnés à Saint Jean Cap/La Ciotat (11 288 g, lots algues égouttées mais non rincées) et Agde (8 500 g, lots algues égouttées mais non rincées) sont lyophilisés pour conduire respectivement à 4 800 g (poids sec total des lots échantillonnés à Saint Jean Cap/La Ciotat) et 3 200 g de matières sèches algales (poids sec total des lots échantillonnés à Saint Jean Cap/la Ciotat). Chaque lot, traité séparément, est broyé pour conduire à une fine poudre et extrait avec de l’éthanol à 96° sous ultrasons (3×15 min) à l’abris de l’air, de la lumière et à température ambiante. Chaque lot est filtré sous vide pour séparer le squelette de l’algue du filtrat. Chaque filtrat est évaporé sous pression réduite (T<35°C) pour conduire à un extrait brut organique (+sels) éthanolique, un total de 233,7 g pour les lots échantillonnés à Saint Jean Cap/La Ciotat et un total de 166,3 g pour les lots échantillonnés à Agde.Batches of algae sampled in Saint Jean Cap/La Ciotat (11,288 g, drained but not rinsed algae batches) and Agde (8,500 g, drained but not rinsed algae batches) are freeze-dried to yield respectively 4,800 g (weight total dry weight of the batches sampled in Saint Jean Cap/La Ciotat) and 3,200 g of dry algal materials (total dry weight of the batches sampled in Saint Jean Cap/la Ciotat). Each batch, treated separately, is crushed to produce a fine powder and extracted with ethanol at 96° under ultrasound (3 × 15 min) protected from air, light and at room temperature. Each batch is vacuum filtered to separate the algal skeleton from the filtrate. Each filtrate is evaporated under reduced pressure (T<35°C) to produce a raw organic (+salts) ethanolic extract, a total of 233.7 g for the batches sampled in Saint Jean Cap/La Ciotat and a total of 166 .3 g for batches sampled in Agde.
Chaque extrait brut organique a alors été repris dans un mélange eau/méthanol (30/70), puis soumis à une Extraction liquide/liquide avec des solvants de polarité croissante : cyclohexane puis dichlorométhane et enfin acétate d’éthyle. Each raw organic extract was then taken up in a water/methanol mixture (30/70), then subjected to liquid/liquid extraction with solvents of increasing polarity: cyclohexane then dichloromethane and finally ethyl acetate.
Ces différentes fractions, ainsi que la fraction résiduelle eau/méthanol, ont alors été évaporées sous pression réduite (T<35°C) pour conduire aux masses suivantes : Fraction cyclohexane : 24.2 g – Fraction Dichlorométhane : 7.8 g – Fraction Acétate d’éthyle : 22.8 – Fraction Eau/méthanol : 260 gThese different fractions, as well as the residual water/methanol fraction, were then evaporated under reduced pressure (T<35°C) to yield the following masses: Cyclohexane fraction: 24.2 g – Dichloromethane fraction: 7.8 g – Ethyl acetate fraction : 22.8 – Water/methanol fraction: 260 g
Des analyses HPLC-DAD-DEDL et HPLC-UV-HRMS62 des différentes fractions ont été réalisées. Les résultats en termes d’HPLC-DAD-UV à 214 nm, 254 nm et 280 nm pour les factions cyclohexane (a), dichlorométhane (b) et acétate d’éthyle (c) ont été obtenus et sont présentés en [Fig 1].HPLC-DAD-DEDL and HPLC-UV-HRMS62 analyzes of the different fractions were carried out. The results in terms of HPLC-DAD-UV at 214 nm, 254 nm and 280 nm for the cyclohexane (a), dichloromethane (b) and ethyl acetate (c) factions were obtained and are presented in [Fig 1 ].
Ces résultats montrent que la fraction cyclohexane contient majoritairement des corps gras, ainsi que des pigments tels que de la chlorophylle, très faiblement détectés par HPLC en phase inverse. Les fractions dichlorométhane contiennent quant a elles majoritairement de la caulerpine, ainsi que des corps gras co-élués avec la caulerpine, alors que les fractions acétate d’éthyle semblaient contenir majoritairement des composés polaires non identifiés. Enfin, la fraction eau/méthanol résiduelle semblait contenir majoritairement des sels, ainsi que quelques composés polaires non identifiés. These results show that the cyclohexane fraction mainly contains fatty substances, as well as pigments such as chlorophyll, very weakly detected by reversed phase HPLC. The dichloromethane fractions contain mainly caulerpin, as well as fatty substances co-eluted with caulerpin, while the ethyl acetate fractions seemed to contain mainly unidentified polar compounds. Finally, the residual water/methanol fraction seemed to contain mainly salts, as well as some unidentified polar compounds.
Nous avons également pu noter que les fractions cyclohexane, dichlorométhane et eau/méthanol résiduelle présentaient des profils HPLC-DAD-DEDL sensiblement proches, que l’algue provienne de Saint Jean Cap/La Ciotat ou d’Agde.We were also able to note that the cyclohexane, dichloromethane and residual water/methanol fractions presented significantly similar HPLC-DAD-DEDL profiles, whether the algae came from Saint Jean Cap/La Ciotat or Agde.
PurificationPurification
Sur les fractions dichlorométhane est réalisé une phase de purification, pour obtenir de la caulerpine pure. Pour cela, des colonnes chromatographiques silice diol sont réalisées sur :
- 1 g (C1) et 550 mg (C2) de fraction, de manière automatisée (à l'aide de la PuriFlash)
- 6 g (C3) de fraction, de manière manuelle, par impossibilité de purifier une quantité si importante par PuriFlash
- 1 g (C1) and 550 mg (C2) fraction, automatically (using PuriFlash)
- 6 g (C3) of fraction, manually, due to the impossibility of purifying such a large quantity by PuriFlash
Après dépôt de l’échantillon en haut de la colonne, nous avons alors utilisé différents solvants de polarité croissante selon la méthode d’élution suivante :
After depositing the sample at the top of the column, we then used different solvents of increasing polarity according to the following elution method:
| Volume de colonne | % Cyclohexane | % Acetate d’éthyle | % Méthanol |
| 0 | 100 | 0 | 0 |
| 2 | 100 | 0 | 0 |
| 12 | 0 | 100 | 0 |
| 14 | 0 | 100 | 0 |
| 24 | 0 | 0 | 100 |
| 29 | 0 | 0 | 100 |
| Column volume | % Cyclohexane | % Ethyl acetate | % Methanol |
| 0 | 100 | 0 | 0 |
| 2 | 100 | 0 | 0 |
| 12 | 0 | 100 | 0 |
| 14 | 0 | 100 | 0 |
| 24 | 0 | 0 | 100 |
| 29 | 0 | 0 | 100 |
Tableau 1 : Méthode d’élution pour purification de la Table 1: Elution method for purification of the
caulerpinecaulerpine
sur colonne on column
Les colonnes chromatographiques sont ensuite analysées par CCM (chromatographie couche mince), afin de rassembler les tubes contenant la caulerpine. Les autres tubes ayant des analyses CMM similaires ont été rassemblés pour obtenir des fractions. The chromatographic columns are then analyzed by TLC (thin layer chromatography), in order to collect the tubes containing the caulerpin. Other tubes with similar CMM analyzes were pooled to obtain fractions.
Différents lavages des fractions contenant la caulerpine sont ensuite réalisés, au moyen de cyclohexane.Various washings of the fractions containing the caulerpine are then carried out, using cyclohexane.
Selon les méthodes de purification utilisées, les quantités de caulerpine obtenues sont présentées dans le tableau 2.
Depending on the purification methods used, the quantities of caulerpine obtained are presented in Table 2.
| Colonne chromatographique | |||
| C1 | C2 | C3 | |
| Méthode de purification | PuriFlash | PuriFlash | PuriFlash |
| Quantité de fraction dichlorométhane utilisée (g) | 1 | 0,550 | 6 |
| Quantité de caulerpine obtenue (mg) | 144 | 67 | 765 |
| Chromatographic column | |||
| C1 | C2 | C3 | |
| Purification method | PuriFlash | PuriFlash | PuriFlash |
| Quantity of dichloromethane fraction used (g) | 1 | 0.550 | 6 |
| Quantity of caulerpine obtained (mg) | 144 | 67 | 765 |
Tableau 2 : Quantité de Table 2: Quantity of
caulerpinecaulerpine
obtenue selon les fractions purifiées obtained according to the purified fractions
En parallèle, une colonne chromatographique silice diol sur 3.5 g de fraction cyclohexane a été réalisée, de manière automatisée (à l’aide de la PuriFlash), selon la même méthode d’élution. Seuls 15 mg de caulerpine pure ont pu être obtenus.In parallel, a silica diol chromatographic column on 3.5 g of cyclohexane fraction was carried out in an automated manner (using the PuriFlash), using the same elution method. Only 15 mg of pure caulerpine could be obtained.
L’isolement de la caulerpine est confirmée par les analyses HPLC-DAD-DEDL, HPLC-UV-HRMS et RMN. The isolation of caulerpin is confirmed by HPLC-DAD-DEDL, HPLC-UV-HRMS and NMR analyses.
L’analyse HPLC-DAD-DEDL a permis de confirmer la pureté de la molécule, le chromatogramme obtenu est présenté à la .The HPLC-DAD-DEDL analysis made it possible to confirm the purity of the molecule, the chromatogram obtained is presented in the .
La formule brute de la caulerpine, C24H18N2O4, a été confirmée par analyse par spectrométrie de masse haute résolution en mode positif HRESI(+)MS (ion pseudomoléculaire [M+H]+ de m/z 399,1315 ; Δppm = -7,52). L’ensemble de ces données spectrales (HRMS, RMN), couplé aux données de la bibliographie, a permis d’identifier la structure comme étant celle de la caulerpine.The crude formula of caulerpin, C 24 H 18 N 2 O 4 , was confirmed by high-resolution positive-mode mass spectrometry analysis HRESI(+)MS (pseudomolecular ion [M+H] + of m/z 399, 1315; Δppm = -7.52). All of these spectral data (HRMS, NMR), coupled with data from the bibliography, made it possible to identify the structure as that of caulerpin.
Exemple Example
22
: Évaluation de la composition cosmétique de soin anti-âge de la peau selon l’invention, : Evaluation of the cosmetic composition for anti-aging skin care according to the invention,
sur l’expression de gènes au sein d’explants de peau humaine.on gene expression in human skin explants.
L’étude est réalisée par le laboratoire Syntivia.The study is carried out by the Syntivia laboratory.
1. OBJECTIF DE L’ETUDE 1. OBJECTIVE OF THE STUDY
L’objectif de l’étude est d’étudier l’efficacité de la composition selon l’invention sur un modèle ex-vivo prospectif de type cosmétogénomique. The objective of the study is to study the effectiveness of the composition according to the invention on a prospective ex-vivo model of cosmetogenomic type.
La technologie RT-qPCR microfluidique sera utilisée. La puce utilisée permet dans cette étude de faire l'analyse d’un produit en triplicata versus 90 gènes sur explants de peau.Microfluidic RT-qPCR technology will be used. The chip used in this study makes it possible to analyze a product in triplicate versus 90 genes on skin explants.
2. PROTOCOLE DE TEST GENOMIQUE 2. GENOMIC TESTING PROTOCOL
2.1 Modèle biologique 2.1 Biological model
Le test a été mené sur explants de peau : une biopsie de peau baignée dans une matrice solide et nourrissante tandis que sa surface épidermique est conservée en contact avec l'air. La biopsie de la peau est fermement ancrée dans la matrice et scellée pour empêcher toute diffusion latérale de formulation destinée a une application topique. The test was carried out on skin explants: a skin biopsy bathed in a solid and nourishing matrix while its epidermal surface is kept in contact with air. The skin biopsy is firmly anchored in the matrix and sealed to prevent any lateral diffusion of formulation intended for topical application.
Les explants sont issus d’une abdominoplastie de femme de 50 ans correspondant a un phototype de II sur l’échelle de Fitzpatrick. The explants come from an abdominoplasty of a 50-year-old woman corresponding to a phototype of II on the Fitzpatrick scale.
2.2 Évaluation des produits 2.2 Product evaluation
L’expérience a été menée en triplicata (n=3) dans les conditions suivantes :
- Explant de peau non traité
- Explant de peau + solvant (90% eau/10% éthanol)
- Explant de peau + caulerpineThe experiment was carried out in triplicate (n=3) under the following conditions:
- Untreated skin explant
- Skin explant + solvent (90% water/10% ethanol)
- Skin explant + caulerpine
- Explant de peau non traité
- Explant de peau + solvant (90% eau/10% éthanol)
- Explant de peau + caulerpineThe experiment was carried out in triplicate (n=3) under the following conditions:
- Untreated skin explant
- Skin explant + solvent (90% water/10% ethanol)
- Skin explant + caulerpine
Les produits ont été préparés comme suit : The products were prepared as follows:
Solvant : Solvent:
Prendre 100 μl d’éthanol et ajouter 900μl d’eau = 10% éthanol/90% eau. Ce produit sera dépose sur explant en topique (10μl, 48h). Take 100 μl of ethanol and add 900 μl of water = 10% ethanol/90% water. This product will be applied topically to the explant (10 μl, 48 hours).
Caulerpine :Caulerpine:
Prendre 3mg de caulerpine pure disponible et ajouter 300 μl d’éthanol = 10 mg/ml de composé pur dans 100% éthanol
Puis prendre 100μl de caulerpine pure 10mg/ml et ajouter 900μl d’eau = 1 mg/ml de composé pur dans 10% éthanol/90% eau.
Ce produit sera déposé sur explant en topique (10μl, 48h). Take 3mg of pure available caulerpine and add 300 μl of ethanol = 10 mg/ml of pure compound in 100% ethanol
Then take 100μl of pure caulerpine 10mg/ml and add 900μl of water = 1 mg/ml of pure compound in 10% ethanol/90% water.
This product will be applied topically to the explant (10 μl, 48 hours).
Puis prendre 100μl de caulerpine pure 10mg/ml et ajouter 900μl d’eau = 1 mg/ml de composé pur dans 10% éthanol/90% eau.
Ce produit sera déposé sur explant en topique (10μl, 48h). Take 3mg of pure available caulerpine and add 300 μl of ethanol = 10 mg/ml of pure compound in 100% ethanol
Then take 100μl of pure caulerpine 10mg/ml and add 900μl of water = 1 mg/ml of pure compound in 10% ethanol/90% water.
This product will be applied topically to the explant (10 μl, 48 hours).
Les explants ont été traités avec le produit durant 2 jours. A l’issus de la phase de culture, les explants ont été retirés de leurs inserts et les ARNm ont été extraits. Ces ARNs ont ensuite été reverse-transcrits en cDNA.
Enfin, les étapes spécifiques de préparation pour la puce (96 gènes) selon le protocole de Fluidigm sont entreprises. Une étape de pré-amplification en présence de l’ensemble des amorces utilisées sur la puce est réalisée. Chaque échantillon d’ADNc préamplifié est ensuite disposé dans une plaque de 96 puits suivant le plan de plaque avec le mix permettant la PCR en temps réel. En parallèle sur une autre plaque 96 puits chaque paire d’amorces est disposée dans un puits suivant le plan de plaque. Ensuite chaque mix est déposé de part et d’autre de la puce. Le mélange des deux mix est effectué par l’IFC Controller puis la puce est disposée dans le BioMark pour réaliser la PCR en temps réel. The explants were treated with the product for 2 days. At the end of the culture phase, the explants were removed from their inserts and the mRNAs were extracted. These RNAs were then reverse-transcribed into cDNA.
Finally, the specific preparation steps for the chip (96 genes) according to the Fluidigm protocol are undertaken. A pre-amplification step in the presence of all the primers used on the chip is carried out. Each preamplified cDNA sample is then placed in a 96-well plate following the plate plan with the mix allowing real-time PCR. In parallel on another 96-well plate, each pair of primers is placed in a well following the plate plane. Then each mix is placed on either side of the chip. The two mixes are mixed by the IFC Controller then the chip is placed in the BioMark to carry out real-time PCR.
Enfin, les étapes spécifiques de préparation pour la puce (96 gènes) selon le protocole de Fluidigm sont entreprises. Une étape de pré-amplification en présence de l’ensemble des amorces utilisées sur la puce est réalisée. Chaque échantillon d’ADNc préamplifié est ensuite disposé dans une plaque de 96 puits suivant le plan de plaque avec le mix permettant la PCR en temps réel. En parallèle sur une autre plaque 96 puits chaque paire d’amorces est disposée dans un puits suivant le plan de plaque. Ensuite chaque mix est déposé de part et d’autre de la puce. Le mélange des deux mix est effectué par l’IFC Controller puis la puce est disposée dans le BioMark pour réaliser la PCR en temps réel. The explants were treated with the product for 2 days. At the end of the culture phase, the explants were removed from their inserts and the mRNAs were extracted. These RNAs were then reverse-transcribed into cDNA.
Finally, the specific preparation steps for the chip (96 genes) according to the Fluidigm protocol are undertaken. A pre-amplification step in the presence of all the primers used on the chip is carried out. Each preamplified cDNA sample is then placed in a 96-well plate following the plate plan with the mix allowing real-time PCR. In parallel on another 96-well plate, each pair of primers is placed in a well following the plate plane. Then each mix is placed on either side of the chip. The two mixes are mixed by the IFC Controller then the chip is placed in the BioMark to carry out real-time PCR.
2.5 Méthode d’analyse des résultats 2.5 Method of analyzing results
La spécificité de chaque couple de primer est vérifiée pour toutes les conditions par analyse des courbes de dissociation et les points problématiques présentant des doubles pics sont retirés de l’analyse. Chaque CT est ensuite ramené aux gènes de référence et à la condition cellulaire contrôle pour calculer le ∆∆CT et l’expression relative est calculée en fonction du ∆∆CT grâce a la formule 2-∆∆CT. The specificity of each primer pair is verified for all conditions by analysis of the dissociation curves and problematic points presenting double peaks are removed from the analysis. Each CT is then returned to the reference genes and the control cell condition to calculate the ∆∆CT and the relative expression is calculated as a function of the ∆∆CT using the formula 2-∆∆CT.
Pour chaque condition, l’erreur standard à la moyenne (SEM) est calculée et les points avec des SEM trop importantes (>40% d’écart entre la SEM et la moyenne des 3 valeurs) sont retirés de l’analyse. Les résultats sont exprimés en pourcentage de surexpression ou de sous-expression par rapport a la condition de référence. For each condition, the standard error of the mean (SEM) is calculated and the points with too large SEMs (>40% difference between the SEM and the mean of the 3 values) are removed from the analysis. The results are expressed as percentage of overexpression or underexpression compared to the reference condition.
Les gènes sont ensuite classés par activité biologique pour faciliter la lecture. The genes are then classified by biological activity for easier reading.
3. RESULTATS : EFFET DES PRODUITS SUR L'EXPRESSION DES GENES 3. RESULTS: EFFECT OF PRODUCTS ON GENE EXPRESSION
Les résultats sont présentés ci-dessous. L’expression basale de chaque gène est a 100%, sont présentés ici les modifications d’expression génique supérieures a 50% d’induction et inférieures a 50% d’inhibition. The results are presented below. The basal expression of each gene is 100%; the changes in gene expression greater than 50% induction and less than 50% inhibition are presented here.
Les gènes suivants sont surexprimés The following genes are overexpressed
concernant l’anti-âge curatif : regarding curative anti-aging:
Concernant la Synthèse et structure de la Matrice ExtraCellulaire (Derme) :
- COL1A1 +120%
- FBN2 +80%
- LOXL1 +280%
- PLOD3 +90%
- COL1A1 +120%
- FBN2 +80%
- LOXL1 +280%
- PLOD3 +90%
La caulerpine démontre une augmentation de l’expression de nombreux gènes en lien avec la Synthèse et la structure de la Matrice ExtraCellulaire (Derme)Caulerpin demonstrates an increase in the expression of numerous genes linked to the Synthesis and structure of the ExtraCellular Matrix (Dermis)
Concernant la cohésion et la Lame Basale :
- CD44 +50%
- PXN+80%
- SDC4 +90%
- CD44 +50%
- PXN+80%
- SDC4 +90%
La caulerpine démontre une augmentation de l’expression de nombreux gènes en lien avec la cohésion et la Lame Basale.Caulerpin demonstrates an increase in the expression of numerous genes related to cohesion and the Basal Lamina.
Les gènes suivants sont surexprimés concernant l’anti-âge The following genes are overexpressed regarding anti-aging
préventifpreventive
: :
Concernant la Survie, la Croissance et le renouvellement cellulaire :
- HBEGF +150%
- INSR +60%
- TP63 +50%
- HBEGF +150%
- INSR +60%
- TP63 +50%
Ces gènes sont liés aux activités suivantes :
- HBEGF : Facteur de croissance qui participe au renouvellement de l'épiderme
- INSR : Récepteur de l'insuline impliqué dans le renouvellement de la peau, la synthèse des constituants du derme et la différenciation épidermique
- TP63 : TP63 est une protéine impliquée dans le renouvellement des kératinocytes et des fibroblastes, elle protège les cellules de la senescence et participe à la différenciation.
- HBEGF: Growth factor which participates in the renewal of the epidermis
- INSR: Insulin receptor involved in skin renewal, synthesis of dermis constituents and epidermal differentiation
- TP63: TP63 is a protein involved in the renewal of keratinocytes and fibroblasts, it protects cells from senescence and participates in differentiation.
La caulerpine démontre une augmentation de l’expression de nombreux gènes en lien avec la survie, la croissance et le renouvellement cellulaire.Caulerpin demonstrates an increase in the expression of numerous genes linked to cell survival, growth and renewal.
Concernant la protection antioxydante :
- GLRX +80%
- HMOX1 +130%
- SOD2 +230%
- GLRX +80%
- HMOX1 +130%
- SOD2 +230%
La caulerpine démontre une augmentation de l’expression de nombreux gènes en lien avec la protection antioxydante.Caulerpin demonstrates an increase in the expression of numerous genes linked to antioxidant protection.
Les gènes suivants sont surexprimés concernant l’anti-âge The following genes are overexpressed regarding anti-aging
préventif et curatif, en lien avec la différenciation cellulaire et la fonction barrièrepreventive and curative, linked to cellular differentiation and barrier function
: :
- CASP14 +170%CASP14 +170%
- IVL +80%IVL +80%
- LOR+80%LOR+80%
- TGM1 +230% TGM1 +230%
La caulerpine démontre une augmentation de l’expression de nombreux gènes en lien avec différenciation cellulaire et la fonction barrière.Caulerpin demonstrates an increase in the expression of numerous genes linked to cellular differentiation and barrier function.
5. CONCLUSION GLOBALE DE L’ETUDE 5. OVERALL CONCLUSION OF THE STUDY
La caulerpine montre des effets positifs en anti-âge, en particulier dans la différenciation cellulaire et la fonction barrière, la protection antioxydante, la survie, la croissance et le renouvellement cellulaire, et la synthèse et structure de la matrice extracellulaire.Caulerpin shows positive effects in anti-aging, particularly in cell differentiation and barrier function, antioxidant protection, cell survival, growth and renewal, and extracellular matrix synthesis and structure.
- Y. Viano, Recherche de molécules non-toxiques actives en antifouling à partir d’organismes marins de Méditerranée, Thèse pour le grade de Docteur de l’Université du Sud Toulon-Var, soutenue le 16/06/2010, École Doctorale des Sciences Chimiques (ED 250).Y. Viano, Research of non-toxic molecules active in antifouling from Mediterranean marine organisms, Thesis for the degree of Doctor of the University of the South Toulon-Var, defended on 06/16/2010, Doctoral School of Sciences Chemicals (ED 250).
- L. Cavas, Y. Baskin, K. Yurdakoc, N. Olgun, Antiproliferative and newly attributed apoptotic activities from an invasive marine alga: Caulerpa racemosa var. cylindracea, Journal of Experimental Marine Biology and Ecology, 2006 ; 339 : 111-119. L. Cavas, Y. Baskin, K. Yurdakoc, N. Olgun, Antiproliferative and newly attributed apoptotic activities from an invasive marine alga: Caulerpa racemosa var. cylindracea, Journal of Experimental Marine Biology and Ecology, 2006; 339: 111-119.
- M. Verlaque, C. Durand, J.M. Huisman, C-F. Boudouresque, Y. Le Parco, On the Identity and origin of the Mediterranean invasive Caulerpa racemosa (Caulerpales, Chlorophyta), European Journal of Phycology, 2003 ; 38 (4) : 325-339. M. Verlaque, C. Durand, JM Huisman, CF. Boudouresque, Y. Le Parco, On the Identity and origin of the Mediterranean invasive Caulerpa racemosa (Caulerpales, Chlorophyta), European Journal of Phycology, 2003; 38 (4): 325-339.
- D. Pesando, R. Lemée, C. Ferrua, P. Amade, J-P. Girard, Effects of caulerpenyne, the major toxin from Caulerpa taxifolia on mechanisms related to sea urchin egg cleavage, Aquatic toxicology, 1996 ; 35 : 139-155.D. Pesando, R. Lemée, C. Ferrua, P. Amade, J-P. Girard, Effects of caulerpenyne, the major toxin from Caulerpa taxifolia on mechanisms related to sea urchin egg cleavage, Aquatic toxicology, 1996; 35:139-155.
- A.S.R. Anjaneyulu, C.V.S. Prakash, K.V.S. Raju, U.V. Mallavadhani, Isolation of new aromatic derivatives from marine algal species Caulerpa racemosa, Journal of Natural Product, 1992 ; 55 : 496-499.A.S.R. Anjaneyulu, C.V.S. Prakash, K.V.S. Raju, U.V. Mallavadhani, Isolation of new aromatic derivatives from marine algal species Caulerpa racemosa, Journal of Natural Product, 1992; 55: 496-499.
- J.P. Vidal, D. Laurent, S.A. Kabore, E. Rechencq, M. Boucaud, J.P. Girard, R. Escale, J.C. Rossi, Caulerpin, caulerpicin, Caulerpa scalpellliformis : comparative acute toxicity study, Botanica Marina, 1984 ; 27 : 533-537.J.P. Vidal, D. Laurent, S.A. Kabore, E. Rechencq, M. Boucaud, J.P. Girard, R. Escale, J.C. Rossi, Caulerpin, caulerpicin, Caulerpa scalpellliformis: comparative acute toxicity study, Botanica Marina, 1984; 27:533-537.
- N.S. Sarma, M.S.R. Krishna, Sk.G. Pasha, Marine Algal natural products: Contributions from India in the global context, Indian Journal of Chemistry B, 2006 ; 45 : 433-449.N.S. Sarma, M.S.R. Krishna, Sk.G. Pasha, Marine Algal natural products: Contributions from India in the global context, Indian Journal of Chemistry B, 2006; 45:433-449.
- N.R.P.V. Macedo, M.S. Ribeiro, R.C. Villaça, W. Ferreira, A.M. Pinto, V.L. Teixeira, C. Cirne-Santos, I.C.N.P. Paixão, V. Giongo, Caulerpin as a potential antiviral drug against herpes simplex virus type 1, Brasilian Journal of Pharmacognosy, 2012 ; 22 (4) : 861-867N.R.P.V. Macedo, M.S. Ribeiro, R.C. Villaça, W. Ferreira, A.M. Pinto, V.L. Teixeira, C. Cirne-Santos, I.C.N.P. Paixão, V. Giongo, Caulerpin as a potential antiviral drug against herpes simplex virus type 1, Brasilian Journal of Pharmacognosy, 2012; 22 (4): 861-867
- L.H. Cavalcante-Silva, A.C. de Carvalho Correja, J.M. Barbosa-Filho, B.A. da Silva, B.V. de Oliveira Santos, D.P. de Lira, S.C. Sousa, G.E. de Miranda, F. de Andrade Cavalcante, M.S. Alexandre-Moreira, Spasmolytic effect of caulerpine involves blockade of Ca2+ influx on guinea pig ileum, Marine Drugs, 2013 ; 11 : 1553-1564.de Miranda, F. de Andrade Cavalcante, M.S. Alexandre-Moreira, Spasmolytic effect of caulerpine involves blockade of Ca2+ influx on guinea pig ileum, Marine Drugs, 2013; 11:1553-1564.
- C.S. Vairappan, Antibacterial activity of major secondary metabolites: found in for species of edible green macroalgae genus Caulerpa, Asian Journal of Microbiology, Biotechnology and Environmental Sciences, 2004 ; 6 : 197-201.C.S. Vairappan, Antibacterial activity of major secondary metabolites: found in for species of edible green macroalgae genus Caulerpa, Asian Journal of Microbiology, Biotechnology and Environmental Sciences, 2004; 6:197-201.
- A.S.R. Anjaneyulu, C.V.S. Prakash, U.V. Mallavadhani, Two caulerpin analogues and a sequiterpene from Caulerpa racemosa, Phytochemistry, 1991 ; 30 (9) : 3041-3042.A.S.R. Anjaneyulu, C.V.S. Prakash, U.V. Mallavadhani, Two caulerpin analogues and a sequiterpene from Caulerpa racemosa, Phytochemistry, 1991; 30 (9): 3041-3042.
- E.T.de Souza, D.P. de Lira, A.C. de Queiroz, D.J.C. da Silva, A.B. de Aquino, E.A.C. Mella, V.P. Lorenzo, G.E.C. de Miranda, J.X. de Araújo-Júnior, M.C. de Oliveira Chaves, J.M. Barbosa-Filho, P.F. de Athayde- Filho, B.V. de Oliveira Santos, M.S. Alexandre-Moreira, The antinociceptive and anti-inflammatory activities of caulerpine, a bisindole alkaloid isolated from seaweeds of the genus Caulerpa, Marine Drugs, 2009 ; 7 : 689-704.de Souza, D.P. de Lira, A.C. de Queiroz, D.J.C. da Silva, A.B. de Aquino, E.A.C. Mella, V.P. Lorenzo, G.E.C. de Miranda, J.X. de Araújo-Júnior, M.C. de Oliveira Chaves, J.M. Barbosa-Filho, P.F. de Athayde-Filho, B.V. de Oliveira Santos, M.S. Alexandre-Moreira, The antinociceptive and anti-inflammatory activities of caulerpine, a bisindole alkaloid isolated from seaweeds of the genus Caulerpa, Marine Drugs, 2009; 7:689-704.
- F.D. Rocha, A.R. Soares, P.J. Houghton, P.J. Houghton, R.C. Pereira, M.A.C. Kaplan, V.L. Teixeira, Potential cytotoxic activity of some Brazilian Seaweeds on Human Melanoma Cells, Phytotherapy Research, 2007 ; 21 : 170-175.F.D. Rocha, A.R. Soares, P.J. Houghton, P.J. Houghton, R.C. Pereira, M.A.C. Kaplan, V.L. Teixeira, Potential cytotoxic activity of some Brazilian Seaweeds on Human Melanoma Cells, Phytotherapy Research, 2007; 21:170-175.
- M.F. Raub, J.H. Cardellina, J.G. Schwede, The green algal pigment caulerpine as a plant growth regulator, Phytochemistry, 1987 ; 26 : 619-620.M.F. Raub, J.H. Cardellina, J.G. Schwede, The green algal pigment caulerpin as a plant growth regulator, Phytochemistry, 1987; 26:619-620.
- T. Nagappan, C.S. Vairappan, Nutritional and bioactive properties of three edible species of green algae, genus Caulerpa (Caulerpaceae), J. Appl. Phycol., 2014 ; 26 : 1019-1027.T. Nagappan, C.S. Vairappan, Nutritional and bioactive properties of three edible species of green algae, genus Caulerpa (Caulerpaceae), J. Appl. Phycol., 2014; 26:1019-1027.
- N. Movahhedin, J. Baran, F.F. Azad, A. Barzegari, H. Nazemigeh, Phytochemistry and biologic activities of Caulerpa pellata native to Oman Sea, Iranian Journal of Pharmaceutical Research, 2014 ; 13 (2) : 515-521.N. Movahhedin, J. Baran, F.F. Azad, A. Barzegari, H. Nazemigeh, Phytochemistry and biological activities of Caulerpa pellata native to Oman Sea, Iranian Journal of Pharmaceutical Research, 2014; 13 (2): 515-521.
- L.S. Costa, G.P. Fidelis, S.L. Cordeiro, R.M. Oliveira, D.A. Sabry, R.B.G. Câmara, L.T.D.B. Nobre, M.S.S.P. Costa, J. Almeida-Lima, E.H.C. Farias, E.L. Leite, H.A.O. Rocha, Biological activities of sulfated polysaccharides from tropical seaweeds, Biomedicine and Pharmacotherapy, 2010 ; 64 : 21-28. L.S. Costa, G.P. Fidelis, S.L. Cordeiro, R.M. Oliveira, D.A. Sabry, R.B.G. Câmara, L.T.D.B. Nobre, M.S.S.P. Costa, J. Almeida-Lima, E.H.C. Farias, E.L. Leite, H.A.O. Rocha, Biological activities of sulfated polysaccharides from tropical seaweeds, Biomedicine and Pharmacotherapy, 2010; 64:21-28.
Claims (7)
- Utilisation cosmétique non-thérapeutique d’une composition comprenant de la caulerpine dans un milieu physiologiquement acceptable pour le soin anti-âge d’une zone de la peau, de préférence du visage. Non-therapeutic cosmetic use of a composition comprising caulerpine in a physiologically acceptable medium for the anti-aging care of an area of the skin, preferably the face.
- Utilisation cosmétique non-thérapeutique selon la revendication précédente, où la caulerpine est extraite de Caulerpa Racemosa. Non-therapeutic cosmetic use according to the preceding claim, where caulerpine is extracted from Caulerpa Racemosa .
- Utilisation cosmétique non-thérapeutique selon l’une quelconque des revendications précédentes, dans laquelle la caulerpine est présente à une concentration entre 0,01 % et 10 %, de préférence entre 0,1% et 5 %, de manière encore plus préférée 1%, en poids de la composition.Non-therapeutic cosmetic use according to any one of the preceding claims, in which the caulerpine is present at a concentration between 0.01% and 10%, preferably between 0.1% and 5%, even more preferably 1%. , by weight of the composition.
- Utilisation cosmétique non-thérapeutique selon l’une quelconque des revendications précédentes, où la composition comprend en outre au moins un agent cosmétiquement acceptable choisi parmi les agents apaisants, les agents restructurant, les agents régénérants, les agents revitalisants, les filtres solaires, les agents antirides, les agents hydratants, les agents anti-âges, les agents tensioactifs, les corps gras, les solvants organiques, les agents solubilisant, les agents épaississants et gélifiants, les lissants, les agents renforçant la fermeté, l’élasticité et/ou l’effet barrière de la peau, les antioxydants, les opacifiants, les eaux thermales, les agents matifiants, les filtres chimiques ou minéraux, les oligoéléments, les agents stabilisants, les agents moussants, les parfums, les émulsionnants ioniques ou non, les charges, les séquestrants et les chélateurs, les parfums, les filtres, les huiles essentielles, les matières colorantes, les pigments, les actifs hydrophiles ou lipophiles, les vésicules lipidiques encapsulant un ou plusieurs actifs et/ou les conservateurs.Non-therapeutic cosmetic use according to any one of the preceding claims, where the composition further comprises at least one cosmetically acceptable agent chosen from soothing agents, restructuring agents, regenerating agents, revitalizing agents, sun filters, agents anti-wrinkle agents, moisturizing agents, anti-aging agents, surfactants, fatty substances, organic solvents, solubilizing agents, thickening and gelling agents, smoothing agents, agents reinforcing firmness, elasticity and/or barrier effect of the skin, antioxidants, opacifiers, thermal waters, mattifying agents, chemical or mineral filters, trace elements, stabilizing agents, foaming agents, perfumes, ionic or non-ionic emulsifiers, fillers, sequestrants and chelators, perfumes, filters, essential oils, coloring materials, pigments, hydrophilic or lipophilic active ingredients, lipid vesicles encapsulating one or more active ingredients and/or preservatives.
- Utilisation cosmétique non-thérapeutique selon la revendication précédente, où ledit au moins un agent cosmétiquement acceptable comprend au moins un agent solubilisant choisi parmi : 2,3-butanediol, le 1,2-hexanediol, l’acétate d’éthyle, le 2-propanol, le propylène glycol, le pentylène glycol, et le dichlorométhane, de préférence une association 1,2-hexanediol/dichlorométhane ou pentylène glycol/dichlorométhane. Non-therapeutic cosmetic use according to the preceding claim, where said at least one cosmetically acceptable agent comprises at least one solubilizing agent chosen from: 2,3-butanediol, 1,2-hexanediol, ethyl acetate, 2- propanol, propylene glycol, pentylene glycol, and dichloromethane, preferably a 1,2-hexanediol/dichloromethane or pentylene glycol/dichloromethane combination.
- Utilisation cosmétique non-thérapeutique selon l’une quelconque des revendications 4 et 5, où ledit filtre solaire est choisi parmi l’homosalate, l’oxybenzone, l’ensulizole, l’ecamsul, l’avobenzone, l’acide benzylidene camphor sulfonic, l’octocrylène, le polyacrylamidomethyl benzylidène camphor, l’ octinoxate, le peg 25-PABA, le PABA, l’isomamyl p- methoxycinnamate, l’octyl triazone, le drometrizole trisiloxane, diethylhexyl butamido triazone, ethylhexyl salicilate, ethylhexyl dimethyl PABA, 4-methylbenzylidene camphor, le 3-benzylidène camphor, l’octisalate, le padimate o, isoamyl p-Methoxycinnamate, benzophenone-4, le méthylène bis-benzotriazolyl tetra- methylbutylphenol, disodium phenyl dibenzimidazole tetrasulfonate, le bis-ethylhexyloxyphenol methoxyphenyl triazine, le polysilicone-15, le dioxyde de titane, l’oxyde de zinc, le butyl méthoxydibenzoylméthane, l’octyl-méthoxycinnamate, le salicylate d'octyle et/ou le diethylamino hydroxybenzoyl hexyl benzoate.Non-therapeutic cosmetic use according to any one of claims 4 and 5, where said sunscreen is chosen from homosalate, oxybenzone, ensulizole, ecamsul, avobenzone, benzylidene camphor sulfonic acid, octocrylene, polyacrylamidomethyl benzylidene camphor, octinoxate, peg 25-PABA, PABA, isomamyl p- methoxycinnamate, octyl triazone, drometrizole trisiloxane, diethylhexyl butamido triazone, ethylhexyl salicilate, ethylhexyl dimethyl PABA, 4 -methylbenzylidene camphor, 3-benzylidene camphor, octisalate, padimate o, isoamyl p-Methoxycinnamate, benzophenone-4, methylene bis-benzotriazolyl tetra- methylbutylphenol, disodium phenyl dibenzimidazole tetrasulfonate, bis-ethylhexyloxyphenol methoxyphenyl triazine, polysilicone -15, titanium dioxide, zinc oxide, butyl methoxydibenzoylmethane, octyl-methoxycinnamate, octyl salicylate and/or diethylamino hydroxybenzoyl hexyl benzoate.
- Utilisation cosmétique non-thérapeutique selon l’une quelconque des revendications précédentes, où ladite composition cosmétique est formulée sous forme de crème, d'une pommade, d’un onguent, d’un baume, d’un masque, d'un lait, d'une lotion, d'un sérum, d’un spray, d'une pâte, d'une mousse, d'un aérosol, d’un stick, d’un shampooing, d’un après-shampooing, de patchs, d'une solution aqueuse hydroalcoolique ou huileuse, d'une émulsion huile-dans-eau ou eau-dans-huile ou multiple, d'un gel aqueux ou huileux, d'un produit anhydre liquide, pâteux ou solide, et/ou d'une dispersion d'huile dans une phase aqueuse à l'aide de sphérules, ces sphérules pouvant être des nanoparticules polymériques telles que les nanosphères et les nanocapsules ou des vésicules lipidiques de type ionique et/ou non-ionique.Non-therapeutic cosmetic use according to any one of the preceding claims, where said cosmetic composition is formulated in the form of a cream, an ointment, an ointment, a balm, a mask, a milk, a lotion, a serum, a spray, a paste, a mousse, an aerosol, a stick, a shampoo, a conditioner, patches, an aqueous hydroalcoholic or oily solution, an oil-in-water or water-in-oil or multiple emulsion, an aqueous or oily gel, an anhydrous liquid, pasty or solid product, and/or a dispersion of oil in an aqueous phase using spherules, these spherules being able to be polymeric nanoparticles such as nanospheres and nanocapsules or lipid vesicles of ionic and/or non-ionic type.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2004010558A (en) * | 2002-06-10 | 2004-01-15 | Noevir Co Ltd | Antioxidant and skin care preparation for external use containing the same |
| JP2004149454A (en) * | 2002-10-30 | 2004-05-27 | Okinawa Pref Gov | Preparation, cosmetic, food product or food additive using antitumor active ingredient contained in caulerpa lentillifera j. agardh |
| ITMI20101406A1 (en) * | 2010-07-28 | 2012-01-29 | Neptys Ltd | PREPARATION FOR TOPICAL USE |
| BRPI1009162A2 (en) * | 2010-11-25 | 2015-08-18 | Univ Fed De Alagoas Ufal | Caulerpine-containing pharmaceutical composition for the treatment of inflammatory diseases and pain |
| JP2017128540A (en) * | 2016-01-21 | 2017-07-27 | ▲徳▼豐銘國際股▲分▼有限公司 | Sea grape extract inhibiting allergy, method for preparing the same, and application of the same |
-
2022
- 2022-07-07 FR FR2206982A patent/FR3137573A1/en active Pending
-
2023
- 2023-07-06 WO PCT/EP2023/068799 patent/WO2024008902A1/en unknown
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2004010558A (en) * | 2002-06-10 | 2004-01-15 | Noevir Co Ltd | Antioxidant and skin care preparation for external use containing the same |
| JP2004149454A (en) * | 2002-10-30 | 2004-05-27 | Okinawa Pref Gov | Preparation, cosmetic, food product or food additive using antitumor active ingredient contained in caulerpa lentillifera j. agardh |
| ITMI20101406A1 (en) * | 2010-07-28 | 2012-01-29 | Neptys Ltd | PREPARATION FOR TOPICAL USE |
| BRPI1009162A2 (en) * | 2010-11-25 | 2015-08-18 | Univ Fed De Alagoas Ufal | Caulerpine-containing pharmaceutical composition for the treatment of inflammatory diseases and pain |
| JP2017128540A (en) * | 2016-01-21 | 2017-07-27 | ▲徳▼豐銘國際股▲分▼有限公司 | Sea grape extract inhibiting allergy, method for preparing the same, and application of the same |
Non-Patent Citations (18)
| Title |
|---|
| A.S.R. ANJANEYULUC.V.S. PRAKASHU.V. MALLAVADHANI: "Two caulerpin analogues and a sequiterpene from Caulerpa racemosa", PHYTOCHEMISTRY, vol. 30, no. 9, 1991, pages 3041 - 3042, XP026631811, DOI: 10.1016/S0031-9422(00)98248-7 |
| C.S. VAIRAPPAN: "Antibacterial activity of major secondary metabolites: found in for species of edible green macroalgae genus Caulerpa, Asian Journal of Microbiology", BIOTECHNOLOGY AND ENVIRONMENTAL SCIENCES, vol. 6, 2004, pages 197 - 201 |
| CANTARINO SARAH J. ET AL: "Microwave irradiation is a suitable method for caulerpin extraction from the green algae Caulerpa racemosa (Chlorophyta, Caulerpaceae)", NATURAL PRODUCT RESEARCH, vol. 36, no. 8, 23 November 2020 (2020-11-23), GB, pages 2149 - 2153, XP093026419, ISSN: 1478-6419, DOI: 10.1080/14786419.2020.1844684 * |
| D. PESANDOR. LEMÉEC. FERMAP. AMADEJ-P. GIRARD: "Effects of cau-lerpenyne, the major toxin from Caulerpa taxifolia on mechanisms related to sea urchin egg cleavage", AQUATIC TOXICOLOGY, vol. 35, 1996, pages 139 - 155 |
| E.L. LEITEH.A.O. ROCHA: "Biological activities of sulfated polysaccharides from tropical seaweeds", BIOMEDICINE AND PHARMACOTHERAPY, vol. 64, 2010, pages 21 - 28, XP026822685 |
| E.T.DE SOUZAD.P. DE LIRAA.C. DE QUEIROZD.J.C. DA SILVAA.B. DE AQUINOE.A.C. MELLAV.P. LORENZOG.E.C. DE MIRANDAJ.X. DE ARAÛJO-JÛNIOR: "The antinociceptive and anti-inflammatory activities of caulerpine, a bisindole alkaloid isolated from seaweeds of the genus Caulerpa", MARINE DRUGS, vol. 7, 2009, pages 689 - 704, XP009143582, DOI: 10.3390/md7040689 |
| J.C. ROSSI: "Caulerpin, caulerpicin, Caulerpa scalpellliformis : comparative acute toxicity study", BOTANICA MARINA, vol. 27, 1984, pages 533 - 537 |
| JOURNAL OF NATURAL PRODUCT, vol. 55, 1992, pages 496 - 499 |
| L. CAVASY. BASKINK. YURDAKOCN. OLGUN: "Antiproliferative and newly at-tributed apoptotic activities from an invasive marine alga: Caulerpa racemosa var. cylindracea", JOURNAL OF EXPERIMENTAL MARINE BIOLOGY AND ECOLOGY, vol. 339, 2006, pages 111 - 119 |
| L.H. CAVALCANTE-SILVAA.C. DE CARVALHO CORREJAJ.M. BARBOSA-FILHOB.A. DA SILVAB.V. DE OLIVEIRA SANTOSD.P. DE LIRAS.C. SOUSAG.E. DE M: "Spasmolytic effect of caulerpine involves blockade of Ca2+ influx on guinea pig ileum", MARINE DRUGS, vol. 11, 2013, pages 1553 - 1564 |
| M. VERLAQUEC. DURANDJ.M. HUISMANC-F. BOUDOURESQUEY. LE PARCO: "On the Identity and origin of the Mediterranean invasive Caulerpa racemosa (Caulerpales, Chlorophyta", EUROPEAN JOURNAL OF PHYCOLOGY, vol. 38, no. 4, 2003, pages 325 - 339 |
| M.F. RAUBJ.H. CARDELLINAJ.G. SCHWEDE: "The green algal pigment caulerpine as a plant growth regulato", PHYTOCHEMISTRY, vol. 26, 1987, pages 619 - 620 |
| MENEZES EDUARDA SOARES ET AL: "ANÁLISE TEMPORAL DE FOCOS DE CALOR NA RESERVA DA BIOSFERA DA SERRA DO ESPINHAÇO", 30 April 2019 (2019-04-30), pages 861 - 867, XP093026295, Retrieved from the Internet <URL:https://www.scielo.br/j/rbfar/a/RMPMTVcNXbvnMSSNxQLTGjq/?format=pdf&lang=en> [retrieved on 20230222], DOI: 10.1590/S0102- * |
| N. MOVAHHEDIN, J. BARAN, F.F. AZAD, A. BARZEGARI, H. NAZEMIGEH: "Phytochemistry and biologie activities of Caulerpa pellata native to Oman Sea,", IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH, vol. 13, no. 2, 2014, pages 515 - 521 |
| N.R.P.V. MACEDOM.S. RIBEIROR.C. VILLAÇAW. FERREIRAA.M. PINTOV.L. TEIXEIRAC. CIRNE-SANTOSI.C.N.P. PAIXÂOV. GIONGO: "Caulerpin as a potential antiviral drug against herpes simplex virus type 1", BRASILIAN JOURNAL OF PHARMACOGNOSY, vol. 22, no. 4, 2012, pages 861 - 867, XP018504520, DOI: 10.1590/S0102-695X2012005000072 |
| N.S. SARMA, M.S.R. KRISHNA, SK.G. PASHA: "Marine Algal natural products: Contributions from India in the global context", INDIAN JOURNAL OF CHEMISTRY B, vol. 45, 2006, pages 433 - 449 |
| T. NAGAPPANC.S. VAIRAPPAN: "Nutritional and bioactive properties of three edible species of green algae, genus Caulerpa (Caulerpaceae", J. APPL. PHYCOL., vol. 26, 2014, pages 1019 - 1027 |
| V.L. TEIXEIRA: "Potential cytotoxic activity of some Brazilian Seaweeds on Human Melanoma Cells", PHYTOTHERAPY RESEARCH, vol. 21, 2007, pages 170 - 175 |
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